medwireNews: Women who experience early menopause, before the age of 49 years, and have increased vascular risk are more susceptible to cognitive decline than other postmenopausal women, suggest results from the Canadian Longitudinal Study on Aging (CLSA).
The research team also found that while a history of estrogen hormone therapy did not affect the combined impact of age at menopause and vascular risk on future cognition, it attenuated the association between earlier age at menopause and lower cognitive scores, irrespective of vascular risk.
“Together, these findings underscore the importance of considering the combined impact of hormonal and vascular risk factors in investigations of female AD [Alzheimer’s disease] risk,” say Jennifer Rabin (University of Toronto, Ontario, Canada) and colleagues in Neurology.
The study involved 8360 women who were at least 2 years post menopause and an equal number of age-matched men as controls from the CLSA Comprehensive Cohort. The cognitive function of the participants was calculated at baseline and at a follow-up visit 3 years later using a composite of scores based on tests of episodic memory, language, and executive function, including the Rey Auditory Verbal Learning Test, Animal Fluency, Controlled Oral Word Association Test, the Stroop Test, and the Mental Alteration Test.
The participants had a baseline mean age of 65.0 years, and women experienced the menopause at a mean age of 50.1 years. More than 95% of both women and men were White, and women had significantly fewer years of education and a generally lower income than men.
Rabin et al found that women had a lower baseline vascular risk than age-matched men, scoring respective means of 1.63 points and 1.80 points on a vascular risk score ranging from 0 to 6, where higher scores indicate higher risk. The score was based on the presence of six risk factors including current smoking, elevated blood pressure, obesity, diabetes, and serum low-density lipoprotein cholesterol levels of 3.5 mmol/L or above.
In linear regression models, the investigators found that earlier age at menopause and higher vascular risk were independently associated with lower follow-up cognitive scores in women. Cognitive scores improved by 0.029 standard deviations (SDs) for every 1 SD increase in age at menopause and worsened by 0.016 SDs for every 1 SD increase in vascular risk score.
The results also showed a synergistic effect between age at menopause and vascular risk, whereby going through the menopause at a younger age significantly exacerbated the negative effect of vascular risk on cognition.
Grouping the women based on age at menopause, Rabin and colleagues found that women who went through the menopause at 35–48 years of age had a mean 0.044 SD decrease in cognitive score with every 1 SD increase in vascular risk score. However, there was no significant association among women who experienced the menopause at 49–52 years of age or 53–65 years of age.
“Considering that female individuals with earlier menopause and higher vascular risk may be at greater risk of dementia, both factors should be considered when developing sex-specific interventions to slow cognitive decline,” write the authors.
The negative effect of vascular risk on cognition was also greater in women who experienced early menopause than in age-matched men, whose cognitive scores at follow-up decreased by 0.035 SD with every 1 SD increase in vascular risk score.
The researchers explain that “endocrine processes may modify sex differences in associations of vascular risk factors with cognitive outcomes, highlighting the need to include female-specific factors in the evaluation of sex differences in dementia risk.”
The strength of the association between increased vascular risk and lower cognitive scores at follow-up was not significantly different when comparing women who had taken hormone therapy containing estrogens (n=2322) and those who had not (n=4992). However, the authors note that the association between early menopause and lower cognitive scores was weaker in women who took hormone therapy relative to those who did not.
“These findings are consistent with studies showing that [hormone therapy] is associated with lower AD risk, especially if initiated in midlife and/or proximal to menopause,” say the researchers, although they caution that they “cannot establish a causal link between [hormone therapy] and cognition.”
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