Earlier menopause (occurring before age 49) coupled with higher risk of cardiovascular disease (CVD) is associated with an increased risk of cognitive problems later in life, a study suggests.
“While CV risk factors are known to increase a person’s risk for dementia, what is lesser known is why women have a greater risk for Alzheimer’s disease than men,” said study author Dr Jennifer Rabin from the University of Toronto in Ontario, Canada.
“We examined if the hormonal change of menopause, specifically the timing of menopause, may play a role in this increased risk. We found that going through this hormonal change earlier in life while also having CV risk factors is linked to greater cognitive problems when compared to men of the same age,” Rabin said.
The researchers evaluated 8,360 postmenopausal women (mean age at baseline 65 years, mean age at menopause 50.1 years) and 8,360 age-matched male participants enrolled in the Canadian Longitudinal Study on Aging. The women were categorized into three groups according to the range of time wherein they experienced menopause: earlier (between 35 and 48 years), average (between 49 and 52 years), and later (between 53 and 65 years). [Neurology 2024;102:e209298]
The investigators reviewed six CV risk factors: hypertension, high low-density lipoprotein-cholesterol, diabetes, obesity, smoking, and prescriptions for antihypertensive medications. They also looked at whether the women had used hormone therapy containing oestrogens. Participants were given a series of thinking and memory tests at the start and end of study and were followed for 3 years.
After adjusting for age and education, the investigators found an interaction between age at menopause and vascular risk – earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores 3 years later (β, 0.013, 95 percent confidence interval [CI], 0.001–0.025; p=0.03).
On stratified analyses, vascular risk was tied to lower cognitive scores in women with earlier menopause (β, -0.044, 95 percent CI, -0.066 to -0.022; p<0.001), but not among those with average (β, -0.007, 95 percent CI, -0.027 to 0.012; p=0.46) or later menopause (β, 0.003, 95 percent CI, -0.020 to 0.025; p=0.82).
Rabin and colleagues noted that the negative association of vascular risk with cognition in women with earlier menopause was stronger than the equivalent association in men.
History of hormone therapy did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (β, -0.005, 95 percent CI, -0.032 to 0.021; p=0.69).
Synergistic effect on cognitive decline
“[Taken together,] our study suggests that earlier menopause may worsen the effects of high CV risk on cognitive decline,” Rabin said.
“Since our study followed participants for only 3 years, more research is needed over longer periods of time. Our findings highlight that age at menopause [and] CV risk should be considered when developing prevention strategies for cognitive decline,” Rabin continued.
However, as the age of menopause was self-reported, this may have limited the findings owing to potential inaccuracy in recalling this age.
Other limitations to take into context were the exclusion of participants who reported a hysterectomy since the age of the procedure was unavailable. Also, there were no data on whether participants had undergone oophorectomy.
“Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in women. These findings have implications for the development of sex-specific dementia prevention strategies,” Rabin and colleagues concluded.