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Summary

Weber et al. [1] reported on a longitudinal study that was conducted over three waves from 2005 through 2016. For the duration of the study, all 85 subjects were in their perimenopause stage (STRAW+10 stage -2 to stage +1a) and evaluated over 400 bi-annual visits. A comprehensive neuropsychological battery was administered, menopausal symptoms evaluated and 17β-estradiol and follicle stimulating hormone (FSH) measured. Multilevel latent profile analysis was used to identify cognitive profiles. All of the recorded visits were sorted into 4 subgroups according to cognitive profiles. After adjusting for STRAW+10 stages and demographic factors, the regression analyses were conducted to determine differences in hormones and symptoms. Most women showed no global impairment, while a significant minority developed weaknesses in verbal learning and memory that were related to both hormonal flux and menopausal symptoms. Compared to women who were cognitively normal, those who had weaknesses in verbal learning and memory were differentiated by less hormonal variability and more sleep disturbance, while women with strength in verbal learning and memory had fewer depressive and vasomotor symptoms (VMS). The investigation showed a significant heterogeneity in cognition during the perimenopause. The authors suggested that cognitive profile analysis should be taken into account to identify at risk populations in order to provide appropriate interventions.

Commentary

In the process of ovarian dysfunction around the age of 50 and longevity of the society, middle-aged women may start to encounter the aging of the organs of the whole body. Since then, women may experience menopausal symptoms (VMS, insomnia, mood disorders) and other changes caused by aging throughout the body. Cognitive impairment is one of the symptoms that cannot be ignored during the menopausal transition. According to the SWAN study in the United States, the self-rated memory decline of menopausal women increased from about 31% in the reproductive stage to 41-44% in the menopausal transition stage, with 41% observed in the postmenopausal stage [2]. Cognitive decline in mid-aged women may be associated with psychosomatic symptoms (i.e depression, anxiety, insomnia). Most previous studies in the field of midlife female cognition have been cross-sectional with small cohorts. It is generally thought that cognitive function during female midlife is influenced by race, education level and life-style profile, which is also consistent with the conclusions of the current commented study. The interesting point of this commented article is the subgroup records according to the cognitive profiles instead of reproductive stages as has also been done in prior research. Only a minor difference was observed between the cognitive profile groups of perimenopausal women, which may have been caused by the group approach used in this study.

With the increase in life expectancy, women demand maintaining not only physical health, but also mental and psychological well-being in the last third of their lives. Generally, midlife women may suffer the decline of cognitive function in the process of ovarian aging. Cognition is a broad term for cerebral cortex function such as attention, working memory, verbal memory, verbal fluency and processing speed. Cognitive problems in menopausal health management should not be ignored. In this article, authors suggest some modifiable factors such as education, sleep symptoms, depression which can be targeted for the preservation of female’s mid-life cognition.

Menopausal health management strategies, including healthy life-style adjustments, and other medical interventions, may in fact reverse at least some aspects of cognitive profile such as verbal memory and visual memory. The efficacy of menopausal hormone therapy (MHT) in the prevention and treatment of dementia is still controversial in different studies [3-6]. Recommendations of the International Menopause Society regarding women’s midlife health and MHT suggest that healthy women who consider MHT for VMS should not worry regarding the possible adverse effects of MHT on cognitive function; whereas MHT should not be used with the sole purpose of enhancing cognitive function alone. Estrogen therapy may be of short-term benefit for surgically menopausal women when initiated at the time of oophorectomy. Studies show that MHT initiated within 10 years of a woman’s last menstrual period has been associated with a reduced risk of Alzheimer’s disease and dementia (Grade B recommendation), while MHT initiated at the age of 65+ increases the risk of dementia (Grade A recommendation).

In addition, it’s important to note that degenerative changes in the brain will also affect cognitive function, which will continue to happen during the rest of life time. Dementia is characterized by severe cognitive decline. Perimenopausal women should be carefully evaluated for cognition impairment and dementia. If a woman has severe cognitive impairment, especially presenting with some special features such as static tremor, bradykinesia, myotonia and postural gait disorder, should be referred to a neurologist. In this sense, multi-disciplinary treatment should be provided in most Chinese menopausal health care clinics, in order to perform early dementia diagnosis and prompt treatment.

Min Luo and Qi Yu
Peking Union Medical College Hospital
Beijing, People’s Republic of China

References

  1. Weber MT, Rubin LH, Schroeder R, Steffenella T, Maki PM. Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates. Climacteric. 2021;24(4):401-407.
    https://pubmed.ncbi.nlm.nih.gov/33759672/
  2. Greendale GA, Wight RG, Huang MH, et al. Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. Am J Epidemiol. 2010;171(11):1214-24.
    https://pubmed.ncbi.nlm.nih.gov/20442205/
  3. Rapp SR, Espeland MA, Shumaker SA, et al.; WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2663-72.
    https://pubmed.ncbi.nlm.nih.gov/12771113/
  4. Gleason CE, Dowling NM, Wharton W, et al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015;12(6):e100183.
    https://pubmed.ncbi.nlm.nih.gov/26035291/
  5. Maki PM, Dennerstein L, Clark M, et al. Perimenopausal use of hormone therapy is associated with enhanced memory and hippocampal function later in life. Brain Res. 2011;1379:232-43.
    https://pubmed.ncbi.nlm.nih.gov/21078303/
  6. Espeland MA, Shumaker SA, Leng I, et al.; WHIMSY Study Group. Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Intern Med. 2013;173(15):1429-36.
    https://pubmed.ncbi.nlm.nih.gov/23797469/

 

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If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui at peter.chedraui@cu.ucsg.edu.ec.

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