Menopausal symptoms linked to higher risk of cognitive decline, dementia

Zahinoor Ismail, MD, FRCPC, neuropsychiatrist and professor at the Cumming School of Medicine at the University of Calgary

Women who experience more symptoms during menopause may face a higher risk of cognitive decline and mild behavioral impairments later in life, according to a new study. These findings, published in PLOS One, suggest a potential link between menopausal symptom burden and dementia risk.¹

“I saw a patient in the emergency room over 20 years ago who had cognitive and psychiatric symptoms that just didn't quite make sense to me,” said Zahinoor Ismail, MD, FRCPC, neuropsychiatrist and professor at the Cumming School of Medicine at the University of Calgary. “I doubled back and explored her menstrual status, and she was perimenopausal, confirmed by hormonal blood work run right in the [Emergency Room]. So, instead of changing her neuropsychiatric medications, which I thought were just fine, I put her on estrogen and her symptoms resolved completely over the next 10 days. This was a stunning outcome to me and stuck with me thereafter.”²

The study, led by researchers from the University of Calgary, analyzed data from 896 postmenopausal women enrolled in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) study. The participants, who had an average age of 64.2 years, completed assessments of their cognitive and behavioral health as well as surveys about their menopausal symptoms. The average age of menopause onset was 49.4 years, with 74.3% of participants reporting at least 1 menopausal symptom​.³

Link between symptoms and cognitive function

Researchers found that women who reported a higher number of perimenopausal symptoms—such as hot flashes, sleep disturbances, mood symptoms, and cognitive difficulties—had poorer cognitive performance, as indicated by higher Everyday Cognition (ECog-II) scores (mean score: 11.1±10.5). They also reported more symptoms of mild behavioral impairment (MBI), with higher MBI-C scores (mean score: 5.4±7.6)​.³

The study used a negative binomial regression model to assess cognitive function and found that each additional menopausal symptom was associated with a 5.37% higher ECog-II score, indicating more consistent symptoms of cognitive dysfunction (95% CI [2.85, 7.97]; p < .001). Similarly, a zero-inflated negative binomial regression model showed that each additional symptom was linked to a 6.09% higher MBI-C score, indicating more behavioral symptoms (95% CI [2.50, 9.80]; p < .001)​.³

Impact of hormone therapy

The study also explored the potential impact of hormone therapy (HT). While HT did not significantly improve cognitive function, it was linked to a 26.9% lower MBI-C score (95% CI [-43.35, -5.67]; p = .016), suggesting it may help reduce behavioral symptoms. Among the 166 participants who used hormone therapy, 11% used combination estrogen-progesterone treatments, while 6.2% used estradiol-based therapy. The most frequently reported perimenopausal symptoms were hot flashes (88%) and night sweats (70%), while chills (14%) and other unspecified symptoms (5%) were least reported​.³

“It's fascinating that there is a link between the menopausal experience and subsequent changes in cognition and behavior. I find that mind blowing”,” said Ismail. He also emphasized the importance of early intervention, stating, “People should know menopause and Alzheimer disease are linked and that earlier consideration of dementia risk can allow time for more preventative interventions.”​²

Broader implications and future research

The study's authors suggest that the loss of estradiol at menopause may be a key factor linking menopausal symptoms to cognitive and behavioral decline. Estradiol is known to support synapse formation and neurogenesis, both of which decline in neurodegenerative diseases like Alzheimer’s. The study highlights the need for additional research to confirm these findings, ideally through longitudinal studies that can assess causality more effectively​.^2,3

The study also pointed to the need for managing other dementia risk factors, such as vascular health and inflammation. “These interventions not only include addressing hormonal status, but also comprise managing vascular risk factors, reducing inflammation from Western diet and environmental toxins, optimizing gut health and gut biome diversity, and supporting social interactions,” said Ismail.²

The authors concluded that a higher menopausal symptom burden may signal susceptibility to cognitive and behavioral changes later in life. “Greater menopausal symptom burden may be associated with greater cognitive and behavioral decline in later life, both risk markers of dementia,” they stated. “Estrogen-based hormone therapy may contribute to mitigating clinical symptoms, particularly behavioral symptoms.”​¹

References:

1. PLOS. Menopause symptoms associated with future memory and neuropsychiatric problems. Eurekalert. March 5, 2025. Accessed March 7, 2025. https://www.eurekalert.org/news-releases/1075182?

2. Interview with Zahinoor Ismail (University of Calgary, Canada; University of Exeter, U.K) and Jasper F.E. Crockford (University of Calgary, Canada). PLOS One. 2025. Accessed March 7, 2025. PDF.

3. 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