Hormonal environment affects cognition independent of age during the menopause transition

Abstract

Context: Cognitive decline is prevalent in aging populations, and cognitive complaints arecommon during menopause. However, the extent of hormonal influence is unclear, particularly when considered independent of the aging process. Objective: We sought to determine differences in cognitive function attributable to menopause, hypothesizing that differences would be associated with reproductive rather than chronological age. Design and Setting: In this cross-sectional study at a university hospital, we combined neuropsychological measures with functional magnetic resonance imaging to comprehensively assess cognitive function. Participants: Sixty-seven menopausal women, aged 42-61 yr, recruited from a population-based menopause study, grouped into menopause stages based on hormonal and cycle criteria (premenopause, perimenopause, and postmenopause), participated in the study. Main Outcome Measures: Neuropsychological and functional magnetic resonance imaging measures of verbal, visual, and executive cognitive function. Results: We found age-independent menopause effects on verbal function. Menopause groups differed in phonemic verbal fluency (F = 3.58, P < 0.019) and regional brain activation (inferior frontal cortex: corrected P < 0.000 right, P < 0.036 left; left prefrontal cortex: P < 0.012); left temporal pole: P < 0.001). Verbal measures correlated with estradiol and FSH (phonemic fluency: R = 0.249, P < 0.047 estradiol, R = -0.275, P < 0.029 FSH; semantic fluency: R = 0.318, P < 0.011 estradiol, R = -0.321, P < 0.010 FSH; right inferior frontal cortex: R = 0.364, P < 0.008 FSH; left inferior frontal cortex: R = -0.431, P < 0.001 estradiol, left prefrontal cortex: R = 0.279, P < 0.045 FSH; left temporal pole: R = -0.310, P < 0.024 estradiol, R = 0.451, P < 0.001 FSH; left parahippocampal gyrus: R = -0.278, P < 0.044 estradiol; left parietal cortex: R = -0.326, P < 0.017 estradiol). Conclusions: Results suggest that verbal fluency mechanisms are vulnerable during the menopausal transition. Targeted intervention may preserve function of this critical cognitive domain. Copyright © 2012 by The Endocrine Society.