Menopause, Brain Anatomy, Cognition and Alzheimer’s Disease

  1. Manuela Costantino
  2. Grace Pigeau
  3. Olivier Parent
  4. Justine Ziolkowski
  5. Gabriel A. Devenyi
  6. Nicole J. Gervais
  7. M. Mallar Chakravarty

  • Curated by eLife

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    eLife assessment

    This study presents useful findings from a large sample of participants from the UK Biobank on the relationship between menopause (including status, type, and age of onset), cognition, neuroanatomical measures derived from magnetic resonance imaging, and Alzheimer's disease. The strength of evidence is incomplete, and the study would benefit from clearer methodological descriptions, more careful consideration of potential confounds, and better theoretical integration with prior work in the field. This paper will be of interest to people working in the fields of cognitive neuroscience, endocrinology, and dementia.

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Abstract

The menopause transition has been repeatedly associated with decreased cognitive performance and increased incidence of Alzheimer’s Disease (AD), particularly when it is induced surgically 1,2 or takes place at a younger age 3,4 . However, there are very few studies that use neuroimaging techniques to examine the effects of these variables in aggregate and in a large sample. Here, we use data from thousands of participants from the UK Biobank to assess the relationship between menopausal status, menopause type (surgical or natural), and age at menopause with cognition, AD, and neuroanatomical measures derived from magnetic resonance imaging. We find that for brain and cognitive measures, menopausal status, menopause type and age at surgical menopause do not impact the brain; but that there is a positive correlation between anatomy, cognition and age at non-surgical menopause. These results do not align with previous reports in the literature with smaller samples. However, we confirm that both early and surgical menopause are associated with a higher risk of developing AD, indicating that early and abrupt ovarian hormone deprivation might contribute to the development of the disorder.

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  1. Version published to 10.7554/elife.91038.1 on eLife
  2. Version published to 10.7554/elife.91038 on eLife
  3. eLife

    eLife assessment

    This study presents useful findings from a large sample of participants from the UK Biobank on the relationship between menopause (including status, type, and age of onset), cognition, neuroanatomical measures derived from magnetic resonance imaging, and Alzheimer's disease. The strength of evidence is incomplete, and the study would benefit from clearer methodological descriptions, more careful consideration of potential confounds, and better theoretical integration with prior work in the field. This paper will be of interest to people working in the fields of cognitive neuroscience, endocrinology, and dementia.

  4. eLife

    Reviewer #1 (Public Review):

    Summary:
    Costantino et al report on data from thousands of participants from the UK Biobank whereby they assessed relationships between menopausal status, menopause type (surgical or natural), and age at menopause with cognition, neuroanatomical measures derived from magnetic resonance imaging and Alzheimer's disease (AD) risk.

    Strengths:
    This is a really important field of research. Alzheimer's disease is a leading cause of death in women and better understanding whether hormonal and brain changes associated with the menopause transition are contributing to this risk is a crucial research question. Access to such a large database, with cognitive assessment alongside structural MRI data, is a strength of this study. The authors report a positive association between earlier age of menopause as well as surgical menopause and a higher risk of developing AD. The authors also report associations between age at natural menopause and performances on various cognitive tests. Positive associations were found between the age of menopause and fluid intelligence, numeric memory, and pair matching.

    Weaknesses:
    The manuscript would benefit from further clarification about the sample and descriptions of analyses. At the moment, it is difficult to determine whether the conclusions align with the results. In terms of the method, this is a cross-sectional analysis, with different subgroups selected depending on the research question and model. Some further clarification on the full sample and the participants selected for each analysis would be helpful. Some clarification on how menopause status and AD diagnosis were determined would be helpful. The results and discussion refer to menopause having an impact on specific cognitive tasks - the domains that these tasks assess would be worthy of some discussion.

  5. eLife

    Reviewer #2 (Public Review):

    Summary:
    In this paper, the authors investigated the relationship between menopause (including status, type, and age of onset) with measures of brain health, including cognition, Alzheimer's disease (including age of onset), and structural brain imaging.

    Strengths:
    A key strength is the use of propensity matching to address the confound of age. However, further clarification and justification regarding the study design, methodology, reporting, and discussion of the results is required.

    Weaknesses:
    Overall, the strength of evidence is uncertain/incomplete, given the methodological limitations present in the design, analyses, and reporting of results. The findings are useful, however, much of the relevant literature in this area is missing and the findings have therefore not been appropriately contextualised nor compared with previous results, including those using the same dataset.

  6. Version published to 10.1101/2022.10.18.512730v1 on bioRxiv