A team of researchers from the Tohoku University Graduate School of Medicine and Tokyo Metropolitan Institute of Medical Science found that women who entered menopause before the age of 40 had worse cognitive outcomes than women who entered menopause after the age of 50. This finding may be useful for clinicians, when assessing their patient's risk of developing dementia.
These findings were published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association on April 15, 2025.
The research team chose to investigate this link because dementia disproportionally affects women worldwide, suggesting that dementia may have risk factors that are specific to women. In addition, early menopause is associated with higher risk of depression in later life, which is a known risk factor for dementia. However, direct evidence regarding the impact of earlier menopause on the age-related trajectories of depressive symptoms and cognitive function is scarce.
The team used data from the English Longitudinal Study of Ageing, classifying age at menopause into three categories: <40, 40-49, and ≥50 years. The study included 4,726 women and 4,286 men who were assessed in measures of cognitive functioning such as orientation, immediate and delayed recall, and verbal fluency. The team tested the association between sex and age at menopause, and cognitive functioning two years later after adjusting baseline modifiable risk factors for dementia.
"When looking for associations, we want to rule out as many other modifiable risk factors for dementia as possible," explains lead author Miharu Nakanishi (Tohoku University Graduate School of Medicine), "Since early menopause increases the risk of depression, which then increases the risk of dementia, we had to control for this factor to determine if early menopause in of itself was a direct risk factor."
After controlling for baseline outcome measures and other covariates (such as other modifiable dementia risk factors), menopause at <40 years, compared with ≥50 years, was significantly associated with worse 2-year follow-up orientation, as well as immediate and delayed recall. Cognitive function in women who entered menopause at ≥50 years old was actually better than the comparison group of men. Hormone replacement therapy (HRT) (a treatment to minimize menopausal symptoms) was not associated with cognitive function.
The results imply that women who experience early menopause may constitute a sex-specific high-risk group for cognitive decline. Further research is warranted to elucidate the underlying mechanisms of the relationship between levels of female hormones and cognitive function.
"Understanding this relationship in-depth could potentially help us design treatments that delay the onset of dementia in at-risk patients," says Nakanishi.