Different effects of cardiometabolic syndrome on brain age in relation to gender and ethnicity

Sung Hoon Kang, Mengting Liu, Gilsoon Park, Sharon Y. Kim, Hyejoo Lee, William Matloff, Lu Zhao, Heejin Yoo, Jun Pyo Kim, Hyemin Jang, Hee Jin Kim, Neda Jahanshad, Kyumgmi Oh, Seong Beom Koh, Duk L. Na, John Gallacher, Rebecca F. Gottesman, Sang Won Seo, Hosung Kim

Research output: Contribution to journalArticlepeer-review


Background: A growing body of evidence shows differences in the prevalence of cardiometabolic syndrome (CMS) and dementia based on gender and ethnicity. However, there is a paucity of information about ethnic- and gender-specific CMS effects on brain age. We investigated the different effects of CMS on brain age by gender in Korean and British cognitively unimpaired (CU) populations. We also determined whether the gender-specific difference in the effects of CMS on brain age changes depending on ethnicity. Methods: These analyses used de-identified, cross-sectional data on CU populations from Korea and United Kingdom (UK) that underwent brain MRI. After propensity score matching to balance the age and gender between the Korean and UK populations, 5759 Korean individuals (3042 males and 2717 females) and 9903 individuals from the UK (4736 males and 5167 females) were included in this study. Brain age index (BAI), calculated by the difference between the predicted brain age by the algorithm and the chronological age, was considered as main outcome and presence of CMS, including type 2 diabetes mellitus (T2DM), hypertension, obesity, and underweight was considered as a predictor. Gender (males and females) and ethnicity (Korean and UK) were considered as effect modifiers. Results: The presence of T2DM and hypertension was associated with a higher BAI regardless of gender and ethnicity (p < 0.001), except for hypertension in Korean males (p = 0.309). Among Koreans, there were interaction effects of gender and the presence of T2DM (p for T2DM*gender = 0.035) and hypertension (p for hypertension*gender = 0.046) on BAI in Koreans, suggesting that T2DM and hypertension are each associated with a higher BAI in females than in males. In contrast, among individuals from the UK, there were no differences in the effects of T2DM (p for T2DM*gender = 0.098) and hypertension (p for hypertension*gender = 0.203) on BAI between males and females. Conclusions: Our results highlight gender and ethnic differences as important factors in mediating the effects of CMS on brain age. Furthermore, these results suggest that ethnic- and gender-specific prevention strategies may be needed to protect against accelerated brain aging.

Original languageEnglish (US)
Article number68
JournalAlzheimer's Research and Therapy
Issue number1
StatePublished - Dec 2023
Externally publishedYes


  • Brain age
  • Cardiometabolic syndrome
  • Ethnicity
  • Gender

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cognitive Neuroscience


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