Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.
In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
What about menstrual history and Alzheimer’s disease?
According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.
Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.
As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.
What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.
In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
What of the neuroprotective effects of endogenous estrogen?
“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.
“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.
Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.