Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis

Abstract

Many theories of cognitive aging are based on evidence that dopamine (DA) declines with age. Here, we performed a systematic meta-analysis of cross-sectional positron emission tomography and single-photon emission-computed tomography studies on the average effects of age on distinct DA targets (receptors, transporters, or relevant enzymes) in healthy adults (N = 95 studies including 2611 participants). Results revealed significant moderate to large, negative effects of age on DA transporters and receptors. Age had a significantly larger effect on D1- than D2-like receptors. In contrast, there was no significant effect of age on DA synthesis capacity. The average age reductions across the DA system were 3.7%-14.0% per decade. A meta-regression found only DA target as a significant moderator of the age effect. This study precisely quantifies prior claims of reduced DA functionality with age. It also identifies presynaptic mechanisms (spared synthesis capacity and reduced DA transporters) that may partially account for previously unexplained phenomena whereby older adults appear to use dopaminergic resources effectively. Recommendations for future studies including minimum required samples sizes are provided.

Keywords: Dopamine; Healthy aging; Meta-analysis; Receptors; Synthesis capacity; Transporters.

Figure 1

Forest plot for studies describing adult age differences in D1-like receptors (multivariate REM with 5 studies and 106 individual subjects). The position of the diamond on the x-axis indicates the effect size (Pearson’s correlation coefficient) between age and kinetic measure for each study and its size corresponds to the weight each study had in the analysis. The grey bars indicate the 95% CI of the effect size. The polygons summarize the sample size weighted effect (also for subregions) with its width representing the 95% CI.

Figure 2

Forest plot for studies describing adult age differences in D2 receptors (multivariate REM with 47 studies and 1213 single subjects). The position of the diamond on the x-axis indicates the effect size (Pearson’s correlation coefficient) between age and kinetic measure for each study and its size corresponds to the weight each study had in the analysis. The grey bars indicate the 95% CI of the effect size. The polygons summarize the sample size weighted effect (also for subregions) with its width representing the 95% CI.

Figure 3

Forest plot for studies describing adult age differences in DA transporter (univariate REM with 33 studies and 1046 single subjects). The position of the diamond on the x-axis indicates the effect size (Pearson’s correlation coefficient) between age and kinetic measure for each study and its size corresponds to the weight each study had in the analysis. The grey bars indicate the 95% CI of the effect size. The polygons summarize the sample size weighted effect (also for subregions) with its width representing the 95% CI.

Figure 4

Forest plot for studies describing adult age differences in DA synthesis capacity (multivariate REM with 13 studies and 278 single subjects). The position of the diamond on the x-axis indicates the effect size (Pearson’s correlation coefficient) between age and kinetic measure for each study and its size corresponds to the weight each study had in the analysis. The grey bars indicate the 95% CI of the effect size. The polygons summarize the sample size weighted effect (also for subregions) with its width representing the 95% CI.

Figure 5

Comparison of average correlations with age (horizontal line within polygon) as well as 95% CIs (polygon height) for DA D1-like receptors, transporters (DAT), D2-like receptors, and synthesis capacity (SC). Dotted line indicates age effect of zero. * significant differences at p < .01 (Cumming, 2009).

Figure 6

Scatterplots depicting the relationship between age and kinetic measure (z-standardized within study) for D1- and D2-like receptors, DA transporters (DAT), and DA synthesis capacity (SC). A linear, a quadratic, and an exponential function were fit to the data.