Early Menopause Was Associated with Increased Risk of Cognitive Decline, Depression within 2 Years
The findings suggest that women who experience early menopause (age <40 vs >50 years) may constitute a sex-specific high-risk group for cognitive decline.
Women who experience menopause before age 40 are at significantly higher risk for both cognitive decline and depressive symptoms later in life, according to a large longitudinal study published in Alzheimer’s & Dementia.1
The analysis, which followed more than 9,000 adults in England, found that early menopause was associated with worse cognitive outcomes across multiple domains compared to menopause at age 50 or later. These associations held even after adjusting for depressive symptoms, lifestyle factors, and baseline cognitive function, according to study authors.1
Women are disproportionately affected by dementia worldwide, a potential indicator of sex-specific risk factors,2 according to lead author Miharu Nakanishi, PhD, associate professor, department of psychiatric nursing, Tohoku University Graduate School of Medicine, and colleagues. There is increasing interest in menopause as a risk factor for dementia specific to women as well.3 Nakanishi et al also note the link now established between early menopause and depression and the observed link between depression and dementia.
"When looking for associations, we want to rule out as many other modifiable risk factors for dementia as possible," Nakanishi said in a news release.4 “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 and of itself was a direct risk factor. Understanding this relationship in-depth could potentially help us design treatments that delay the onset of dementia in at-risk patients.”4
Age Matters
Nakanishi et al reported that women who experienced menopause at younger than age 40 and from 40-49 years demonstrated more severe depressive symptoms and lower cognitive function scores compared to those with menopause at age 50 or older. After adjusting for baseline outcomes and covariates, earlier menopause significantly correlated with worse 2-year follow-up depressive symptoms.1
Menopause in the age group to experience it earliest was significantly associated with worse cognitive function at the 2-year follow up, including worse orientation, immediate/delayed recall, and verbal fluency than in the group with menopause at 50 or older. The researchers found a significant correlation between baseline depressive symptoms and worse cognitive function, noting that the associations remained consistent when classifying menopause age into quartiles and after excluding participants with baseline dementia.1
Nakanishi’s team reported that longer reproductive periods correlated with less severe depressive symptoms and better immediate recall and verbal fluency, perhaps related to the protective effect of estrogen during that time. More live births associated with improved verbal fluency, while miscarriages, stillbirths, and abortions were correlated with lower orientation.
Menopause secondary to surgery and use of hormone replacement therapy (HRT) were both associated with more severe depressive symptoms, with pre-menopausal HRT initiation showing significantly worse outcomes than no HRT use at all.
Depressive symptoms among men were less severe at follow-up than among women with menopause at 50 years or older. However, cognitive function in women in that menopausal age group was better than among men.1
The researchers found a significant correlation between baseline depressive symptoms and worse cognitive function, noting that the associations remained consistent when classifying menopause age into quartiles and after excluding participants with baseline dementia.
Nakanishi et al used data from the English Longitudinal Study of Ageing, examining 4726 women and 4286 men over multiple waves of data collection. Variables included age at menopause, other reproductive factors, cognitive function, depressive symptoms and a range of covariates. Other reproductive factors included type of menopause, hormone replacement therapy use, years of reproductive periods, and the number of miscarriages, stillbirths, and abortions. Age at menopause was stratified into 3 groups: younger than 40 years, 40–49 years, and 50 years and older.
Cognitive assessments included orientation, immediate and delayed recall, and verbal fluency. Investigators used the 8-item Center for Epidemiologic Studies Depression Scale to evaluate depressive symptoms.
While the authors controlled for a wide range of covariates—including health behaviors, comorbid conditions, and sociodemographic variables—the study had several limitations. Most notably, the average age of study entry was mid-50s, meaning menopause had already occurred for many participants. Cognitive function was measured at only a 2-year interval and did not include extensive neuropsychological testing. Genetic data such as APOE ε4 status were not incorporated, and information on antidepressant use or HRT composition was lacking.
Still, the authors emphasized their findings indicate a need for additional research into targeted dementia prevention strategies.
“Prevention of early menopause would be beneficial in addressing the disproportionate dementia risk for women,” they said, advocating for interventions focused on modifiable lifestyle factors such as smoking, alcohol use, and physical inactivity.1 Moreover, “Dementia risk-reduction strategies should consider women who experience early menopause as a sex-specific high-risk group. Further research is warranted to elucidate the underlying mechanisms,” they concluded.1
