Choline kinase alpha genotype is related to hippocampal brain volume and cognition in postmenopausal women.

This study examined how single nucleotide polymorphisms (SNPs) related to choline synthesis and metabolism, processes largely regulated by estrogen, influenced hippocampal volume and neuropsychological function following menopause. We investigated the effect of choline kinase alpha (CHKA) genotype on brain volume and neuropsychological performance in postmenopausal women. The effect alleles of certain CHKA SNPs (rs6591331 T, rs10791957 A) are associated with varied responses to choline deficiency and delegation of choline to physiological pathways. The presence of these alleles was hypothesized to correlate with worse cognitive performance in women after menopause. Results from structural MRI scans revealed larger right hippocampal volumes in subjects with a T/T CHKA rs6591331 genotype compared to A/A subjects. Delayed memory scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were lower in subjects with T/T genotypes compared to those with the A/T genotype and the A/A genotype. Based on these findings, we proposed a CHKA-dependent mechanism present within the brain to compensate for the decreased estrogen and biosynthesized choline associated with menopause.

Dopamine-dependent cognitive processes after menopause: the relationship between COMT genotype, estradiol, and working memory.

The present study examined how a gene related to functioning of the dopaminergic system, catechol-O-methyltransferase (COMT), and estradiol were related to brain functioning in healthy postmenopausal women. Participants were 118 healthy, cognitively normal postmenopausal women between the ages of 50-60 years. All women provided a blood sample for COMT and estradiol analyses and underwent a magnetic resonance imaging scan. Working memory performance and related brain activation were measured with BOLD functional magnetic resonance imaging during the N-back task. Results were examined across each COMT genotype and a median split was performed on the circulating estradiol levels to create high and low estradiol groups for each genotype. COMT genotype and estradiol level were hypothesized to be proxy measures for brain dopamine levels with the Met/Met and high estradiol group having the most dopamine and Val/Val and low estradiol group having the least dopamine. The functional magnetic resonance imaging results showed that the N-back task activated the expected bilateral frontal and bilateral parietal working memory network. However, no main effects of COMT genotype or estradiol group were found. There was COMT-estradiol interaction found in a small area of decreased activation in the right precentral gyrus (Brodmann Area 6) that was related to the increasing hypothesized dopamine level. Specifically, women with a Met/Met genotype in the high estradiol group had the least activation in this frontal lobe working memory region. Women with a Val/Val genotype in the low estradiol group had greater activation in this region relative to the other groups. Performance on the N-back task did not show any group differences. These data indicate that after menopause COMT genotype and potentially the menopause-related changes to the dopaminergic system are not related to cognition. Future studies should examine how the relationship between COMT, estradiol, and cognition around the menopause transition as there appear to be differences in this relationship for premenopausal and postmenopausal women.

The role of estradiol in schizophrenia diagnosis and symptoms in postmenopausal women.

Schizophrenia is one of the most common mental illnesses in our society, affecting up to 1% of the population. There has been an increase in the number of people who are living longer with schizophrenia and people are being diagnosed later in life, with the majority of those later diagnoses being in women. In addition, there is a spike in diagnoses after women go through menopause, suggesting an important role for gonadal steroids in the disease. This paper examined aspects of aging and schizophrenia in the context of hormonal changes in women. With the rising prevalence rate of schizophrenia and the unique challenges that women face while aging with this disease, the idea of estrogen as a therapeutic agent to reduce symptom severity in postmenopausal women should be considered. In addition, we reviewed literature that suggests that estrogen interacts with the dopaminergic system to affect cognition and this should be studied further in older women with schizophrenia. Positive results in these studies have the potential to drastically improve the aging process for postmenopausal women with schizophrenia.