Background: Menopause is associated with altered memory circuitry function and decreased glucose metabolism, resulting in a period of vulnerability in women. Here, we assessed the impact of metabolic health, in relation to sex and reproductive aging, on memory performance and cellular aging in midlife.

Methods: 103 participants (48M:55F) underwent metabolic and memory assessments at ages 40-50 and follow-up memory assessments at ages 45-55. Generalized estimating equations were used for analyses.

Results: At ages 40-50, there was no significant relationship between metabolic health and memory (p>0.05). However, women with prediabetic/diabetic levels of HbA1c at ages 40-50 performed significantly worse on memory tasks 5-years later compared to those with lower HbA1c levels (β=-6.32, p<0.01) and differed significantly from men (p<0.01). Further, women with higher HbA1c levels who transitioned to postmenopause during the follow-up period had the worst memory performance 5-years later (β=-1.22, p<0.01) compared with those who remained in pre/perimenopause (p=0.05). Finally, poor metabolic health was also related to accelerated cellular aging in the form of shorter telomere length (β=-0.41, p<0.05).

Conclusions: Results suggest that midlife metabolic health is related to cellular aging and has a greater longitudinal impact on memory performance in women compared to men as women transition through menopause.