There have been attempts to stimulate the
There have been attempts to stimulate the dopaminergic system to influence cognition in women around menopause who have subjective complaints about their cognition by Epperson et al. (Epperson et al., 2011, Epperson et al., 2015). In perimenopausal and postmenopausal women, Epperson et al. found that atomoxetine treatment for 6 weeks compared to placebo improved subjective reports of memory and attention but had no effect on objective performance (Epperson et al., 2011). They also found lisdexamphetamine for 4 weeks compared to placebo improved subjective cognition as well as delayed recall in postmenopausal with menopause-related subjective cognitive decline. Thus, studies are beginning to examine methods other than hormonal treatment after menopause to improve cognition and methods that modulate the dopaminergic system may be useful in this endeavor. It may be the case the personalization of treatments for cognition associated with the hormonal change at menopause may be possible by considering a woman\'s COMT genotype and circulating estradiol. Further work is needed to examine when the COMT-estradiol influence on carnitine palmitoyltransferase functioning and cognition changes as women age through the menopause transition.
Conclusion The present study examined how COMT genotype and estradiol in postmenopausal women were associated with working memory-related brain functioning. The data showed that neither COMT nor postmenopausal estradiol were related to working memory-related brain functioning. There was 1 brain region showing an interaction between COMT and estradiol that showed decreasing activation associated with increasing dopamine. However, there were no relationships between COMT, estradiol, and working memory performance. We propose that this COMT-estradiol relationship may underlie individual differences in cognition before menopause as shown by Jacobs and D\'Esposito (2011). However, in postmenopausal women, the COMT-estradiol interaction appears to be less important in explaining individual differences in cognition. The structural (Volkow et al., 1998, Wong et al., 1984) as well as functional (Backman et al., 2006) changes in the dopaminergic system will continue into old age. Further studies are needed to determine when estradiol\'s relationship with working memory performance changes as its levels decrease after menopause. This information may influence the development of personalized methods for the treatment of cognitive changes after menopause.
Introduction The ability to flexibly adjust behavior to changing environmental demands (cognitive flexibility), and to maintain newly learned behavioral preferences without regressing to previous, and no longer adaptive, response preferences (cognitive stability) form important complementary components of executive function (Diamond, 2013). Patients with schizophrenia and affective disorders have well-established disturbances in cognitive flexibility and stability evident in many studies using the Wisconsin Card Sorting Test (WCST) (Heaton et al., 1994; Merriam et al., 1999). Similar deficits have been reported on a computerized analog of the WCST, the Penn Conditional Exclusion Test (PCET) (Hill et al., 2015). Utilizing translational models of cognition evaluating discrete components of behavioral set shifting mediated by different brain regions may improve the sensitivity of set-shifting tasks for understanding cognitive deficits in psychotic disorders and for evaluating treatment outcomes and genetic associations. Research using animal models has indicated a critical role for the interaction between dopaminergic activity in the prefrontal cortex and striatum in set-shifting. Specifically, cognitive flexibility is impaired by a combination of decreased prefrontal dopamine (DA) and elevated striatal DA, while cognitive stability is impaired in the context of increased prefrontal DA and decreased striatal dopaminergic activity (Amodeo et al., 2014; Ragozzino et al., 2002; Roberts et al., 1994).