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Summary

Rasa Kazlauskaite et al. [1] conducted a 17-years prospective, longitudinal study with the participation of 2,149 women traversing menopause, in order to determine the association between metabolic syndrome (MS) exposure and cognitive function evolution. Women from seven US sites were enrolled in the Study of Women’s Health Across the Nation (SWAN), a study of health and aging during the menopausal transition. MS was diagnosed in 635 women (29.5%), the mean age at their cognitive baseline was 50.7±2.9 years, and 51.6% of women had bleeding patterns consistent with early perimenopause or premenopause. The prevalence of MS was lower among women in premenopause and early perimenopause or treated with hormone therapy. Three domains of cognitive function were evaluated: perceptual speed, episodic memory and working memory. The results were adjusted for sociodemographic, lifestyle, sleep, mood, and menopausal stages/hormone therapy factors and potential confounders in the association between MS and cognitive function scores. The authors found an accelerated decline in perceptual speed, but not in episodic or working memory, in women with MS at midlife, compared with those without exposure to MS. Potential limitations of this study are the evaluation of a limited number of cognitive tests and the lack of information about the overall duration of MS exposure and its consequences on other cognitive domains.

Commentary

MS is a cluster of interrelated conditions, with a high prevalence in the adult population, which increases with age and in the postmenopausal period [2]. The association between MS and diabetes mellitus, insulin resistance, cardiovascular and cerebrovascular diseases is widely recognized [3].MS has also been associated with cognitive dysfunction. Several etiopathogenic factors have been proposed to explain the cognitive impairment associated with the MS and its disorders: chronic inflammation, neuroinflammation, immune dysregulation, oxidative stress, mitochondrial dysfunction, impaired vascular reactivity, and abnormal brain lipid metabolism [4,5]. Reduced visuospatial ability in women with PCOS compared with control subjects was described and was linked to higher levels of HbA1c, suggesting a role for altered glycemic control in cognitive disturbances. (6) Worse cognitive performance in an attentional interference task, which involves executive functions, was previously demonstrated in subjects with MS during exercise compared to controls [7]. Obesity has been clearly identified as an independent factor for cognitive decline and Alzheimer’s Disease [8]. Gut microbiota, metabolic dysfunction and cognitive function have been correlated factors. An unhealthy diet, a sedentary lifestyle, genetics and environmental mechanisms, among others, impact on gut microbiota composition and microbial-derived compounds. Abnormal microbiota leads to increased intestinal permeability and the passage of bacteria and their products through the gastrointestinal mucosa, promoting chronic inflammation, which underlies obesity, metabolic disorders and cognitive dysfunction [9]. Previous reports have shown longitudinal declines in cognitive performance in midlife women [10]. The present study [1] confirms, in a large 17-years prospective, longitudinal study, the association of an accelerated decline in perceptual speed with the MS in women during the menopause transition and postmenopause. This evidence constitutes a new incentive for clinicians to adopt preventive and therapeutic strategies during a woman’s life in order to avoid the consequences of metabolic syndrome and its associated comorbidities.The prime emphasis in management of the metabolic syndrome is to control the modifiable risk factors (obesity, physical inactivity, and atherogenic diet) through lifestyle changes. Specific pharmacological interventions are often needed to control hyperglycemia, hypertension and dyslipidemia. New exciting research shows preclinical evidence for the therapeutic efficacy of central cholinergic stimulation in alleviating obesity-associated inflammation, neuroinflammation, and metabolic derangements [4], intermittent fasting can improve cardiovascular and metabolic risk, through reductions in oxidative damage and inflammation (11). Microbiota modulation may also be a new interesting approach (9).

Sonia Cerdas Pérez
Endocrinologist, Hospital Cima, San José, University of Costa Rica

References

  1. Kazlauskaite R, Janssen I, Wilson RS, et al. Is Midlife Metabolic Syndrome Associated With Cognitive Function Change? The Study of Women’s Health Across the Nation. J Clin Endocrinol Metab. 2020,105:e1093-e1105.
    https://pubmed.ncbi.nlm.nih.gov/32083676/
  2. K. Tserotas & J. E. Blümel. Menopause research in Latin America. Climacteric 2019, 22:17-21.
    https://pubmed.ncbi.nlm.nih.gov/30572731/
  3. Moore, K. J., and Shah, R. Introduction to the Obesity, Metabolic Syndrome, and CVD Compendium. Circulation Research 2020, 126:1475–1476.
    https://pubmed.ncbi.nlm.nih.gov/32437304/
  4. Chang EH, Chavan SS and Pavlov VA. Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities. Front. Neurosci. 2019,13:1-13
    https://pubmed.ncbi.nlm.nih.gov/31024226/
  5. Yates KF, Sweat V, Yau PL, Turchiano MM, Convit A. Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Arterioscler Thromb Vasc Biol. 2012, 32: 2060-2067.
    https://pubmed.ncbi.nlm.nih.gov/22895667/
  6. Brittany Y Jarrett, Natalie Vantman, Reid J Mergler, Eric D Brooks, Roger A Pierson, Donna R Chizen, Marla E Lujan. Dysglycemia, Not Altered Sex Steroid Hormones, Affects Cognitive Function in Polycystic Ovary Syndrome. J Endocr Soc 2019, 3:1858–1868,
    https://pubmed.ncbi.nlm.nih.gov/31583367/
  7. Guicciardi M, Crisafulli A, Doneddu A, Fadda D and Lecis R. Effects of Metabolic Syndrome on Cognitive Performance of Adults During Exercise. Front. Psychol. 2019, 10:1-8
    https://pubmed.ncbi.nlm.nih.gov/31440195/
  8. Farruggia, M. C., Small, D. M. Effects of adiposity and metabolic dysfunction on cognition: A review. Physiology & Behavior. 2019,208: 1-16
    https://pubmed.ncbi.nlm.nih.gov/31194997/
  9. Arnoriaga-Rodríguez, M., Fernández-Real, J.M. Microbiota impacts on chronic inflammation and metabolic syndrome – related cognitive dysfunction. Rev Endocr Metab Disord 2019, 20, 473–480
    https://pubmed.ncbi.nlm.nih.gov/31884557/
  10. Karlamangla AS, Lachman ME, Han W, Huang M, Greendale GA. Evidence for Cognitive Aging in Midlife Women: Study of Women’s Health Across the Nation. PLoS One. 2017,12:e0169008.
    https://pubmed.ncbi.nlm.nih.gov/28045986/
  11. Mattson, M., Moehl, K., Ghena, N. et al. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci 2018,19:81–94.
    https://pubmed.ncbi.nlm.nih.gov/29321682/
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