Impact of Ageing on Memory and Dopaminergic Modulation: A Concurrent MR-PET Study with Fallypride
Poster No:
2442
Submission Type:
Abstract Submission
Authors:
Yeo-Jin Yi1, Jarkko Johansson2, Berta Garcia-Garcia1, Peter Schulze1, Kathrin Baldauf1, Matthew Betts1, Marianne Patt3, Oliver Speck4, Osama Sabri3, Michael Kreißl5, Emrah Düzel6, Dorothea Hämmerer7
Institutions:
1German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Sachsen-Anhalt, 2Department of Radiation Sciences, Umeå, -, 3University Hospital Leipzig, Leipzig, Sachsen, 4German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany, 5University Hospital Magdeburg, Magdeburg, Sachsen-Anhalt, 6Institute of Cognitive Neurology and Dementia Research, Magdeburg, Germany, 7Innsbruck University, Innsbruck, Tirol
First Author:
Co-Author(s):
Introduction:
The dopaminergic system's profound impact on cognitive functions, particularly learning and memory, is well known (Lisman, Grace, & Düzel, 2011; Lisman & Grace, 2005). Dopamine (DA) is in particular essential for encoding and consolidating salient memories-key to our survival (Shohamy & Adcock, 2010). With an ageing population and rising neurodegenerative diseases, deciphering the DA system's memory link is crucial (Bäckman et al., 2010). Our study uses concurrent fMRI and dynamic [18F]fallypride PET imaging to examine age-related changes in D2/D3 receptor function's impact on memory.
Methods:
Thirty-three healthy seniors (age: M=71.48, SD=5.52) underwent two concurrent MR-PET sessions with the high-affinity D2/D3 receptor antagonist [18F]fallypride. During the fMRI-PET sessions, subjects performed a reward task to investigate the link between reward, memory encoding, and DA receptor density. Approximately 15 minutes and 24 hours after the reward task, subjects performed recognition tests. PET data analyses included motion and physiological artefact correction, sMRI parcellation, and the radioactivity curve over time (time-activity curve [TAC]) extraction from regions of interests (Figure 1). Pharmacokinetic analysis of TACs using a simplified reference tissue model quantified the baseline BPND (BPBSL) (Lammertsma & Hume, 1996).
Results:
Partial correlation analyses, controlling for age, revealed significant associations between BPBSL and recognition memory test performance quantified as loglinear D-prime (D'; Hautus 1995). A differential relationship between positive and negative relationships of receptor density and memory for neutral and rewarded stimuli was observed (Figure 2). Specifically, older adults with higher receptor densities in thalamus and nucleus accumbens (NAcc) showed better memory in particular for neutral scenes (thalamus: ρ=0.372, pFDRc=0.012; NAcc: ρ=0.294, pFDRc=0.058). Similarly, older adults with higher D2/D3 receptor density in the putamen showed better memory for reward-associated stimuli (ρ=0.305, p=0.041). On the other hand, higher D2/D3 receptor densities in substantia nigra (SN) and NAcc were related to worse memory for reward-associated stimuli (SN: ρ=-0.307, p=0.041; NAcc: ρ=-0.268, p=0.085).
Conclusions:
Our study delineates the complex relationship between the DA system and memory encoding in ageing adults. We observed significant but varied correlations across different brain regions, which also distinguished memory performance for neutral and reward-associated stimuli. Particularly, enhanced memory for rewarded stimuli seemed particularly linked to higher D2/D3 receptor densities in the putamen, as opposed to findings in the SN and NAcc. In contrast, memory for neutral stimuli appeared to be associated with higher D2/D3 receptor densities in the thalamus and NAcc. These results may indicate a comparatively pronounced role in attention processing structures in the recognition of less the less salient neutral stimuli in ageing. We hope that our observations contribute to a better understanding of ageing memory capacities and underscore the potential of dopaminergic modulation as a target for interventions.
Learning and Memory:
Long-Term Memory (Episodic and Semantic)
Learning and Memory Other
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
PET Modeling and Analysis
Novel Imaging Acquisition Methods:
PET 1
Keywords:
Aging
Brainstem
Cognition
Dopamine
Memory
MRI
Positron Emission Tomography (PET)
1|2Indicates the priority used for review
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Hautus, Michael J. (1995), ‘Corrections for Extreme Proportions and Their Biasing Effects on Estimated Values Ofd′’. Behavior Research Methods, Instruments, & Computers 27 (1): 46–51. https://doi.org/10.3758/BF03203619.
Lammertsma, Adriaan A., and Susan P. Hume. (1996), ‘Simplified Reference Tissue Model for PET Receptor Studies’. NeuroImage 4 (3): 153–58. https://doi.org/10.1006/nimg.1996.0066.
Lisman, John E., and Anthony A. Grace. (2005), ‘The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory’. Neuron 46 (5): 703–13. https://doi.org/10.1016/j.neuron.2005.05.002.
Lisman, John, Anthony A. Grace, and Emrah Duzel. (2011), ‘A neoHebbian Framework for Episodic Memory; Role of Dopamine-Dependent Late LTP’. Trends in Neurosciences 34 (10): 536–47. https://doi.org/10.1016/j.tins.2011.07.006.
Shohamy, Daphna, and R. Alison Adcock. (2010), ‘Dopamine and Adaptive Memory’. Trends in Cognitive Sciences 14 (10): 464–72. https://doi.org/10.1016/j.tics.2010.08.002.