The association between steroid hormones and cognitive performance in adulthood

The aim of this thesis was to investigate whether endogenous estrogen and testosterone were associated with cognitive performance in adulthood and whether hand preference affected the pattern of sex differences in cognitive performance. The analyses in Studies I-IV were based on data from the Betula project in Umeå, Sweden; a population-based longitudinal study on aging and memory. At the second follow-up, there were 3011 participants between 35 and 90 years of age, some entering the project for the first time and others visiting the second or third time.

In Study I, the association between endogenous testosterone and cognitive performance was investigated in men and women. We used (a) a reliable hormone assay, (b) a wide range of cognitive measures to discern regular trends in the data, and (c) participants of a wide age range to explore the hypothesized age-testosterone interaction. The results showed a positive association between testosterone and performance on episodic and spatial tasks for men that increased with age. In contrast, there was a negative trend between testosterone and cognitive performance in women. The results show that testosterone has a sex specific effect on cognition, with opposite directional effects observed for men and women.

The aim of Study II was to investigate whether there were sex differences in cognitive performance in non-right-handed individuals. Given that the bulk of individuals are righthanded, reports of sex differences are based on the majorities cognitive profile. Earlier studies have found an interaction between sex and hand preference in cognitive performance. Results from Study II revealed that there were sex differences in episodic memory, verbal fluency, and spatial ability among right-handed, but not among non-right-handed individuals. Non-right-handed men tended to perform better on verbal tasks and lower on the spatial task in contrast to right-handed men. Furthermore, non-right-handed women showed the reverse pattern, with lower verbal and higher spatial performance as compared to right-handed women. Tentatively, these data suggest atypical lateralization pattern for right-handed and non-right-handed individuals.

In Studies III and IV, the aim was to investigate whether the diminishing levels of estrogen in menopause were associated with cognitive decline. When cross-sectional data was investigated in Study III, no association between menopause phase and cognitive performance was found. In Study IV, longitudinal data was explored to investigate whether cognitive performance changed systematically for women passing through menopause, independent of age-related change in cognition. Results indicate that post-menopausal women show accelerated decline, or less gain, on tasks that measure spatial ability, verbal fluency, and episodic memory. The association between estrogen and accelerated rate of change was most pronounced in normal weight women. This association may reflect the fact that estrogen is largely produced in fat tissue post menopause, with women with higher body mass index (BMI) values having higher levels of estrogen.

This thesis shows that (a) there is a positive association between testosterone and cognitive performance in men, a relationship that increases with increasing age, (b) there are no sex differences in cognition in groups of non-right-handed individuals, (c) cognitive performance does not differ between groups of pre-, peri-, and postmenopausal women, but (d) following menopause, women reveal a higher rate of change for some cognitive measures independent of age-related cognitive change, an effect that is chiefly observed for women with normal BMI.

List of scientific papers

I. Thilers PP, Macdonald SW, Herlitz A (2006). "The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-old men and women." Psychoneuroendocrinology 31(5): 565-76. Epub 2006 Feb 17
https://pubmed.ncbi.nlm.nih.gov/16487665

II. Thilers PP, MacDonald SW, Herlitz A (2007). "Sex differences in cognition: the role of handedness." Physiol Behav 92(1-2): 105-9. Epub 2007 May 21
https://pubmed.ncbi.nlm.nih.gov/17644146

III. Herlitz A, Thilers P, Habib R (2007). "Endogenous estrogen is not associated with cognitive performance before, during, or after menopause." Menopause 14(3 Pt 1): 425-31
https://pubmed.ncbi.nlm.nih.gov/17279058

IV. Thilers PP, MacDonald SW, Nilsson LG, Herlitz A (2009). "Accelerated postmenopausal cognitive decline is restricted to women with normal BMI: Longitudinal evidence from the Betula Project." (Submitted)