March 5, 2025

expert reaction to observational study of severity of menopause symptoms and cognition and behavioural impairment later in life

An observational study published in PLOS One looks at menopause symptom severity and late-life cognitive function and behavioural impairment.

Prof Aimee Spector, Professor of Clinical Psychology of Ageing, UCL, said:

“Some important limitations of this study include the risk of bias in the self-reporting of both menopausal symptoms and cognitive function. The average age of women in the study was 64 – with the oldest being 88 – and the average age of menopause is 49, therefore they are being asked to recall symptoms from a long time before. Further, ‘cognitive function’ was measured by their subjective rating of their own memory rather than the use of objective tests for memory change that could be assessed over time.

“Whilst they found an association; there is no evidence that the menopause symptoms led to the cognitive changes and there could be many possible reasons why people with more menopause symptoms may experience more cognitive changes, such as depression or physical health conditions. I don’t think that the study can tell us anything about menopause symptoms and the risk of dementia, as subjective cognitive complaints do not imply that the person has or will get dementia.”

Dr Sheona Scales, Director of Research at Alzheimer’s Research UK, said:

“This study adds to our understanding of how menopause may relate to brain health for women in later life. It suggests that women who experience more menopausal symptoms, report greater cognitive and behavioural changes as they age. However, this study does not show that these women are more likely to go on to develop dementia.

“Dementia is caused by diseases in the brain, and while menopause could play a role in our brain health, we need more research to understand if and how this influences dementia risk. Some symptoms of menopause, like ‘brain fog’ or forgetfulness, are similar to early dementia symptoms.

“Long-term studies will be key to determining whether menopause-related changes have lasting implications, and whether interventions like hormone replacement therapy could play a protective role.

“With women making up two-thirds of people in the UK living with dementia, it is crucial that we invest in research that explores why women are more at risk of developing the condition. We advise anyone concerned about menopause symptoms or changes in their memory, thinking and behaviour to speak to their doctor for further advice.”

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and President of the British Neuroscience Association said:

“This study by scientists at the University of Calgary looked at data from 896 people and compared menopausal symptom burden with cognitive and behavioural function.  Authors observed that menopausal symptoms were associated with poorer cognitive function and worse behavioural symptoms in mid to late life.  While this study is on a very important topic of why women are at higher risk of dementia than men, there are several important limitations to this work that limit its impact.  This study relied on people self-reporting their symptoms and only looked at a single time point an average of 15 years after menopause onset.  This type of study cannot determine whether the observed higher menopause symptom burden caused the changes in cognition and behaviour.  Further research is needed to understand whether experiences in menopause are linked to dementia risk.”

Prof Robert Howard, Professor of Old Age Psychiatry, UCL Division of Psychiatry, UCL, said:

“Irresponsible reporting of the conclusions of this study could cause considerable anxiety in women who have experienced troubling symptoms during their own the menopause. Hopefully, a little unpacking of what the study actually showed will be reassuring. The results suggest that women who self-reported more severe symptoms associated with their menopause were more likely to subsequently self-report more subjective complaints about their memory, concentration and difficulties with thinking. There are much more likely (and obvious) explanations for this association than the suggestion that a difficult experience of menopause is a risk factor for dementia.”

Prof Eef Hogervorst, Professor of Psychology, Loughborough University, said:

“This is not the first paper to suggest that severe vasomotor symptoms are associated with increased risk for dementia, although this is a contentious area of research. 

“Observational studies cannot indicate causality so we cannot say that more severe menopause symptoms will lead to later cognitive issues or dementia.

“One explanation for this association could be that women have worse sleep or different cardiovascular profiles, both of which could be associated with dementia risk. Women who are stressed can have worse flushes too, which is associated with poorer long-term outcomes for brain and heart. 

“What we do know from research and treatment trials in particular is that healthy lifestyles including some types of exercise, reducing stress, prioritising sleep, healthy diets, not smoking and limiting alcohol are the best ways to reduce vasomotor frequency and severity, can independently improve both quality of life in perimenopausal women and also reduce risk for dementia.” 

Dr Claire Lancaster, Lecturer in the Department of Clinical Neuroscience, Brighton & Sussex Medical School, said:

“This research suggests the number of different menopause symptoms experienced by females in mid-life predicts self-reported cognitive change and mild behavioural symptoms approximately 15-years later. The result is interesting given existing evidence linking vasomotor symptoms specifically to AD pathologies such as amyloid. The authors suggestion a decline in estrogen may affect both brain health directly, plus wider systems (e.g., inflammation, vascular function) which in turn have knock-on effects on brain health certainly warrants future research. 

“When considering this result, however, it is important to note that menopause symptoms are being reported retrospectively by participants, and that participants report whether they experienced the symptom as a simplistic ‘yes’ or ‘no’, rather than the scale collecting information on severity and frequency of menopause symptoms. As such, results may not truly reflect women’s experiences of menopause, specifically their bodies ability to cope with a decline in estrogen. Cognition and behavioural impairment (e.g., apathy, social withdrawal) are also collected via self-report. In general, females in this sample report very little cognitive decline from their past self – as reflected by the mean and standard deviation of scores on the E-Cog II Scale, plus limited behavioural symptoms. For example, cognitively healthy older adults from the ADNI cohort report a mean score of 54 on the E-COG II*, which is far greater than the mean score of 11 reported here.  As such, readers must ask whether the cognitive and behavioural indices reported here truly represent increased risk for dementia as suggested by the authors. This casts doubt on whether data presented here are adequate to claim number of symptoms predicts subsequent dementia risk – on the face of this study alone, I would say no. 

“Whilst the statistics are robust, it is worth noting that moderating health and lifestyle factors weren’t controlled for. For example, physical activity is suggested to improve physiological symptoms of menopause plus is reported to be protective against neurodegenerative disease in later life. Alcohol consumption confers a negative association with menopause symptoms and dementia risk in contrast. This further blurs confusion. 

“The million dollar question when considering sex differences in Alzheimer’s risk is whether hormone replacement therapy can reduce dementia risk. Data reported here suggests there is no real association with HRT use and subjective cognitive change. Research into the effects of HRT on late-life cognition is very inconsistent at present. I would argue this study collects insufficient data about HRT use (e.g., time of onset relative to menopause, duration of use), including the context for it’s use (spontaneous vs. medical menopause) to be able to really comment on this question.  All this being said, the results add to a growing body of research suggesting mid-life endocrine changes are important for cognitive health in later years.”

*https://doi.org/10.1002/dad2.12274

‘Menopausal symptom burden as a predictor of mid- to late-life cognitive function and mild behavioral impairment symptoms: A CAN-PROTECT study’ by Jasper F. E. Crockford et al. was published in PLOS ONE at 19:00 UK time on Wednesday 5^th March. 

DOI: https://doi.org/10.1371/journal.pone.0301165

Declared interests

Prof Aimee Spector: I am leading a review group for the World Health Organisation – their role being to review the evidence of HRT on dementia risk, to inform the new WHO guidelines.

Prof Tara Spires-Jones: I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

Prof Robert Howard: No conflicts of interest.

Prof Eef Hogervorst: I have worked for NICE and ESHRE in non paid positions advising as expert on menopause hormones and the brain. In 2025 I am invited to two European conferences to speak about this topic (ESG and ECNP) where travel and accommodation is reimbursed.

Dr Claire Lancaster: I am a committee member of the Alzheimer’s Research UK South Coast network (voluntary role).

For all other experts, no reply to our request for DOIs was received.