Different dopaminergic circuits defined by D2/D3 receptor availablity patterns show structure-specific links to memory in ageing

  1. Yeo-Jin Yi
  2. Jarkko Johansson
  3. Berta Garcia-Garcia
  4. Peter Schulze
  5. Kathrin Baldauf
  6. Ines Bodewald
  7. Marianne Patt
  8. Swen Hesse
  9. Andeas Schildan
  10. Philipp Genseke
  11. Simone Schenke
  12. Matthew J. Betts
  13. Joel Dunn
  14. Christin Y. Sander
  15. Osama Sabri
  16. Michael C. Kreissl
  17. Oliver Speck
  18. Emrah Düzel
  19. Dorothea Hämmerer
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Abstract

Cognitive ageing is marked by progressive decline in episodic memory and dopaminergic function, yet the extent to which individual differences in dopaminergic system integrity influence memory under motivational contexts remains unclear. In this study, we investigated how baseline D2/D3 receptor availability (BPND 0) in key dopaminergic pathways relates to reward-modulated memory performance in healthy older adults. Thirty-three healthy seniors (aged 64-85) underwent two session concurrent MR-PET imaging with [1F]fallypride involving scene categorisation task with high- and low-motivational contexts. We quantified BPND 0 across nine dopaminergic regions of interest and examined their relationships with recognition memory performance at short (∼15m) and long (∼24h) delays.

Baseline D2/D3 receptor availability showed high test-retest reliability and regionally distinct profiles, suggesting it reflects a stable neurochemical characteristic in healthy ageing, and principal axis factor analysis revealed two partially independent dopaminergic subsystems (dorsal striatal vs mesolimbic) based on interindividual patterns in receptor densities. Region-specific associations further linked D2/D3 receptor availability to distinct memory outcomes. Higher caudate D2/D3 receptor availability was associated with a liberal response bias (increased hits and false alarms both), whereas higher putamen D2/D3 predicted more durable long-term memory retention. Greater thalamic D2/D3 receptor availability correlated with fewer short-term false memories, while greater D2/D3 receptor availability in the amygdala was associated with better recognition at longer delays. In contrast, higher midbrain (substantia nigra and ventral tegmental area) D2/D3 availability which was linked to poorer reward-related memory performance. These findings suggest several complementary dopaminergic circuits supporting episodic memory. Our results highlight dopaminergic neuromodulation as a key factor in cognitive ageing and a potential target for interventions to bolster memory in late life.

Patient consent and ethics approval

All subjects who were included in this study have provided their consent prior to their participation, following the guidelines of the ethics committee at University Hospital Magdeburg in Magdeburg, Germany.

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