Menopause symptoms associated with future memory and neuropsychiatric problems

Women who exhibit more menopausal symptoms are more likely to later have poorer cognitive function and mild behavioral impairments – both markers of dementia. That is the conclusion of a study of 896 postmenopausal females published March 5, 2025, in the open-access journal PLOS One by Zahinoor Ismail of University of Calgary, Canada, and colleagues. 

Females are known to have a three-fold greater risk of developing Alzheimer’s disease and related dementias, and will be disproportionately affected by the increasing global dementia burden. A proposed factor that may confer special risk to females is the loss of estradiol at menopause.

In the new study, researchers used data from the ongoing Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) study. Data on 896 respondents who completed demographic, cognitive, and behavioral assessments and reported being post-menopausal were included. Participants had an average age of 64.2 years and an average age at menopause onset of 49.4 years.

Menopausal symptom burden was assessed by summing the total number of recalled perimenopausal symptoms, including irregular periods, hot flashes, chills, vaginal dryness, weight gain, slowed metabolism, night sweats, sleep problems, mood symptoms, inattention or forgetfulness, and other unnamed symptoms. The study found that women who reported more perimenopausal symptoms had greater cognitive impairment, with higher ECog-II total scores (b [95% confidence interval (CI)] = 5.37 [2.85, 7.97]). They also had more mild behavioral impairment symptoms in mid- to late life, with higher MBI-C total scores (b [95% CI] = 6.09 [2.50, 9.80]). Hormone therapy was not significantly associated with cognitive function but was linked to fewer behavioral symptoms.

The authors conclude that a higher menopausal symptom burden may indicate susceptibility to cognitive and behavioral changes later in life. The study acknowledges the need for further investigation to confirm these findings in a larger dataset, ideally with a longitudinal design to allow for determination of causality. Further segregation of the participants to account for confounding risk factors, including age of menopausal onset or surgical menopause intervention, would also benefit future studies.

The authors add: “Greater menopausal symptom burden may be associated with greater cognitive and behavioral decline in later life, both risk markers of dementia. Estrogen-based hormone therapy may contribute to mitigating clinical symptoms, particularly behavioral symptoms.”

Author interview: https://plos.io/43uIN9x

In your coverage, please use this URL to provide access to the freely available article in PLOS One: https://plos.io/3D8CaP5

Citation: Crockford JFE, Guan DX, Einstein G, Ballard C, Creese B, Corbett A, et al. (2025) Menopausal symptom burden as a predictor of mid- to late-life cognitive function and mild behavioral impairment symptoms: A CAN-PROTECT study. PLoS ONE 20(3): e0301165. https://doi.org/10.1371/journal.pone.0301165

Author countries: Canada, U.K.

Funding: CAN-PROTECT has been supported by Gordie Howe CARES (https://www.gordiehowecares.com/) and the Evans Family fund via the Hotchkiss Brain Institute (https://hbi.ucalgary.ca/) at the University of Calgary. ZI is supported by the UK National Institute for Health and Care Research Exeter Biomedical Research Centre (https://www.exeter.ac.uk/research/biomedicalresearchcentre/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.