The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms

Goran Papenberg; Nina Karalija; Jarkko Johansson; Micael Andersson; Jan Axelsson; Katrine Riklund; Ulman Lindenberger; Lars Nyberg; Lars Bäckman

doi:10.1016/j.cortex.2024.01.014

The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms

Cortex. 2024 Apr 18:176:53-61. doi: 10.1016/j.cortex.2024.01.014. Online ahead of print.

Authors

Goran Papenberg¹, Nina Karalija², Jarkko Johansson³, Micael Andersson², Jan Axelsson³, Katrine Riklund³, Ulman Lindenberger⁴, Lars Nyberg⁵, Lars Bäckman⁶

Affiliations

¹ Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden. Electronic address: goran.papenberg@ki.se.
² Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
³ Department of Diagnostics and Intervention, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden.
⁴ Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany.
⁵ Department of Diagnostics and Intervention, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden.
⁶ Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.

PMID: 38749085
DOI: 10.1016/j.cortex.2024.01.014

Abstract

Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals.

Keywords: BNDF; Dopamine D2 receptors; Episodic memory; Inter-individual differences; KIBRA; Longitudinal; [(11)C]raclopride.