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Alzheimer's disease and related dementias (ADRD) and cardiovascular disease are major women's health issues, and among the leading causes of death in women. Midlife—here defined as the ages of 40 up to 65 years old—is of particular importance for women's brain and cardiovascular health. The neuropathological hallmarks of dementia due to ADRD, including amyloid beta and hyperphosphorylated tau, begin to accumulate at midlife. White matter hyperintensities, indicators of cerebral small vessel damage, can be common even among women in their 50s. Further health considerations in midlife include menopause, a reproductive transition accompanied by adverse changes in cognitive performance, accelerated accumulation of atherosclerosis, and possibly increases cerebrovascular risk, beyond aging alone. Thus, this period is critical for identifying modifiable risk factors that may accelerate the neuropathology of ADRD.

In a recent study published in Alzheimer’s & Dementia, scientists including Rebecca Thurston, PhD (Pittsburgh Foundation Chair in Women's Health and Dementia and Professor of Psychiatry, Clinical and Translational Science, Epidemiology and Psychology), Minjie Wu, PhD (Assistant Professor of Psychiatry), and Howard Aizenstein, MD, PhD (Charles F. Reynolds III and Ellen G. Detlefsen Endowed Chair in Geriatric Psychiatry and Professor of Bioengineering and Clinical and Translational Science), from Pitt Psychiatry, tested the hypothesis that higher carotid intima media thickness, an indicator of subclinical atherosclerosis, would be associated with greater white matter hyperintensities volume among midlife women. 

A cohort of women aged 45 to 67 enrolled in the MsHeart/MsBrain studies (focused on menopause and cardiovascular health, and brain health) underwent carotid artery ultrasound, phlebotomy, and brain magnetic resonance imaging. One hundred and seventy participants had undergone an ultrasound five years earlier.

The investigators found that among midlife women, higher carotid intima media thickness was associated with greater white matter hyperintensities volume. The associations between carotid intima media thickness and white matter hyperintensities volume were most pronounced among women who carried the APOEε4 allele, a group at particular neurocognitive and cardiovascular risk.

“These findings point to the critical interplay between the cardiovascular system and the brain at midlife, and underscore the importance of reducing midlife cardiovascular risk, particularly for APOE ɛ4 carriers, to preserve women’s brain health as they age,” said Dr. Thurston, the study’s corresponding author.

Carotid intima media thickness and white matter hyperintensity volume among midlife women
Thurston RC, Wu M, Barinas-Mitchell E, Chang Y, Aizenstein, H, Derby CA, Maki PM
Alzheimer’s & Dementia. 2023;1–9. https://doi.org/10.1002/alz.12951