Sex Differences in Dopamine D1-type Receptors and Episodic Memory : an Imaging Study Across the Adult Lifespan

Sammanfattning: Identification of the pathways that could be targeted to alleviate ageing-related cognitive decline is of prime importance. One of the most promising target mechanisms is connected to healthy dopaminergic ageing. Extant research suggest that women may exhibit less ageing-related dopamine (DA) decline compared to men, implicating that women may suffer less from dopamine-related cognitive decline. However, to date, shortage of empirical investigations limit firm conclusions of sex differences. In the present work it is hypothesized that: (i) women as compared to men exhibit less aging-related DA losses, and (ii) less aging-related decline of episodic memory (EM), and that (iii) sex differences in episodic memory might be mediated by differences in DA integrity. To that end, sex-related differences in D1-type dopamine receptor (D1DR) integrity and episodic memory were investigated in a healthy cohort of young to old participants (age 20 – 80, n = 180, 50% women) through whole-brain voxel-wise analysis and linear regression models. Firstly, the dorsal caudate was identified as the main region of the EM-D1DR interrelation. Secondly, a significant female advantage was found for EM and D1DR in ageing. Finally, no mediation effect by D1DR on the sex-EM interaction was found. These results indicate the presence of correlational relationships between sex, cognition and D1DR, in ageing. However, D1DR was not found to be the mediating factor in the observed correlations. Future research, preferably using longitudinal design, should further investigate the underpinnings of sex differences in D1DR and EM.