Recently, Thurston et al.  investigated whether vasomotor symptoms (VMS), when rigorously assessed using physiologic measures, were associated among midlife women with greater white matter hyperintensity volume (WMHV). The authors considered a range of potential explanatory factors in these associations and explored whether VMS were associated with the spatial distribution of WMHV. For this, women aged 45-67 (n=226) who were free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were analyzed in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, occipital) and additional covariates including sleep. The investigators found that physiologically-assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest significant associations observed for sleep VMS [24-hour VMS, wake VMS, sleep VMS]. Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep, periventricular and frontal lobe WMHV. The authors conclude that VMS, particularly those occurring during sleep, were associated with greater WMHV. In addition, they recommend the crucial need of finding female-specific midlife markers of poor brain health later in life in order to identify women who warrant early intervention and prevention. VMS have the potential to serve as this female-specific midlife marker of brain health in women.
VMS are commonly regarded just as annoying and uncomfortable side effects of ovarian failure, which may either be temporary and wane within up to several years in the postmenopause, or can be successfully treated by menopausal hormone therapy, but having no otherwise health significance. Contrarily, many recent studies showed that VMS are related to important clinical situations, and therefore the occurrence of VMS should raise attention to potential problems in various body systems. Accumulating evidence indicates that VMS are associated with cardiovascular health and with an increased risk for several chronic diseases, including the metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver diseases, and osteoporosis in peri- and postmenopausal women .
White matter hyperintensities (WMHs) are brain white matter lesions that are hyperintense on fluid attenuated inversion recovery magnetic resonance imaging (FLAIR-MRI) scans. WMHs are commonly seen on brain MRIs in older people, but appear also in certain disease conditions, mainly in neurological and psychiatric disorders . One of the underlying mechanisms is ischemia, expressed as small vessel disease. Larger WMH volumes have been associated with Alzheimer’s disease (AD) and with cognitive decline .
So these are the facts: 1) the menopausal transition has been recognized as an important period for women’s brain health; 2) VMS frequently occur from the early stage of menopause onward; and 3) the existence of WMHs points at a higher risk for cognitive decline. The present commented paper of Thurston et al.  tied all these parameters and investigated the association between VMS, monitored objectively by sternal skin conduction rather than according to women’s subjective report, and WMHs recorded by very accurate MRI scans. Study findings pointed at a clear association between VMS, especially if occurring during sleep , and greater whole brain WMH volume. Such results may indicate that VMS should be considered as a valuable early marker for future cognitive impairment. Understanding the scope of the VMS phenomenon clearly contradicts the previous commonly held belief of its irrelevance to major health issues in various body systems.
Amos Pines, MD
Sackler Faculty of Medicine, Tel-Aviv University, Israel
- Thurston RC, Wu M, Chang YF, Aizenstein HJ, Derby CA, Barinas-Mitchell EA, Maki P. Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women. 2022 Oct 12:10.1212/WNL.0000000000201401. doi: 10.1212/WNL.0000000000201401.
- Ryu KJ, Park H, Park JS, et al. Vasomotor Symptoms: More Than Temporary Menopausal Symptoms. J Menopausal Med. 2020;26(3):147-153.
- Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. 2010;341:c3666.
- Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol. 2015;11(3):157-165.
- Thurston RC, Wu M, Aizenstein HJ, et al. Sleep characteristics and white matter hyperintensities among midlife women. 2020;43(6):zsz298.
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