Sex Differences in the Association Between Midlife Cardiovascular Conditions or Risk Factors With Midlife Cognitive Decline

Neurology. 2022 Feb 8;98(6):e623-e632. doi: 10.1212/WNL.0000000000013174. Epub 2022 Jan 5.


Background and objectives: The prevalence of midlife cardiovascular conditions and risk factors is higher in men than women. Associations between midlife cardiovascular conditions or risk factors and midlife cognitive decline have been reported, but few studies have assessed sex differences in these associations.

Methods: We included 1,857 participants enrolled in the population-based Mayo Clinic Study of Aging who were 50 to 69 years of age at baseline. Participants were evaluated every 15 months by a coordinator, including neurologic evaluation and neuropsychological testing. The neuropsychological testing used 9 tests to calculate global cognitive and domain-specific (memory, language, executive function, and visuospatial skills) z scores. Nurse abstractors reviewed participant medical records to determine the presence of cardiovascular conditions (coronary heart disease, arrhythmias, congestive heart failure) and risk factors (hypertension, diabetes, dyslipidemia, obesity, ever smoking). Linear mixed-effect models evaluated the association between baseline cardiovascular conditions or risk factors and global and domain-specific cognitive decline. Multivariable models adjusted for demographics, APOE genotype, depression, and other medical conditions. Interactions between sex and each cardiovascular condition or risk factor were examined, and results were stratified by sex.

Results: Overall, 1,465 (78.9%) participants had at least 1 cardiovascular condition or risk factor; the proportion of men was higher than women (767 [83.4%] vs 698 [74.5%], p < 0.0001). Cross-sectionally, coronary heart disease and ever smoking were associated with a lower visuospatial z score in multivariable models. Longitudinally, several cardiovascular conditions and risk factors were associated with declines in global and domain-specific z scores but not visuospatial z scores. Most cardiovascular conditions were more strongly associated with cognition among women: coronary heart disease and other cardiovascular conditions were associated with global cognitive decline only in women (all p < 0.05). In addition, diabetes, dyslipidemia, and coronary heart disease were associated with language z score decline only in women (all p < 0.05). However, congestive heart failure was associated with language z score decline only in men (all p < 0.05).

Discussion: Midlife cardiovascular conditions and risk factors are associated with midlife cognitive decline. Moreover, specific cardiovascular conditions and risk factors have stronger associations with cognitive decline in midlife for women than men despite the higher prevalence of those conditions in men.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cognition
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / epidemiology
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Risk Factors
  • Sex Characteristics*