Hormonal Environment Affects Cognition Independent of Age during the Menopause Transition

Context: Cognitive decline is prevalent in aging populations, and cognitive complaints are common 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 parahip-pocampal 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. (J Clin Endocrinol Metab 97: E1686-E1694, 2012)