For men, CHF associated with language decline

Though the frequency of cardiovascular conditions and risk factors is greater in men than women in midlife, those events appear to differentially affect midlife cognitive decline, a cohort study found.

For example, among nearly 1,900 middle-aged patients who were dementia-free at baseline, coronary heart disease (CHD) and other cardiovascular conditions were associated with global cognition decline only in women (P<0.05 for all), reported Michelle Mielke, PhD, of Mayo Clinic in Rochester, Minnesota, and co-authors in Neurology.

Diabetes, dyslipidemia, and CHD were also associated with language z-score decline, again only in women (P<0.05). Congestive heart failure (CHF), however, was associated with language z-score decline only in men (P<0.05).

“Our results show that midlife cardiovascular conditions and risk factors were associated with midlife cognitive decline, but the association is stronger for women,” Mielke said in a statement.

“More research is needed to examine sex differences in the relationships between the cardiovascular risk factors and specific biomarkers of brain disease like white matter hyperintensities, areas of dead tissue, and overall white matter integrity in midlife,” she added. “That may help us better understand the sex-specific mechanisms, by which the cardiovascular conditions and risk factors contribute to cognitive impairment in both women and men.”

Middle-aged adults, especially women, with cardiovascular conditions or risk factors like hypertension and diabetes may represent critical subgroups for early monitoring, Mielke and co-authors noted. “In addition, there is a need to investigate whether the duration and response to treatment for these cardiovascular conditions in men and women may underlie disparities in cognitive and brain aging outcomes,” they wrote.

The team studied 1,857 participants (49.5% men) from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, who were 50 to 69 years old at baseline and who had a first visit between February 2012 and February 2020. All participants were evaluated every 15 months with neuropsychological tests of global and domain-specific (memory, language, executive function, and visuospatial skills) cognitive function reported as z-scores. Mean follow-up was three years and did not differ by sex.

Cardiovascular conditions included coronary heart disease, arrhythmia, congestive heart failure, and “other,” which consisted of peripheral vascular disease and stroke. Cardiovascular risk factors were hypertension, diabetes, dyslipidemia, body mass index, obesity, and smoking. Both were determined from medical records. Models were adjusted for demographics, APOE genotype, depression, and comorbidities.

Overall, 78.9% of participants had at least one cardiovascular condition or risk factor. The proportion of men was higher (83.4% for men versus 74.5% for women, P<0.0001).

Cross-sectionally, coronary heart disease and smoking were associated with a lower visuospatial z score. Longitudinally, several cardiovascular conditions and risk factors were linked to declines in global or domain-specific z scores, but not visuospatial scores.

“In the current analyses, we found midlife cardiovascular conditions and risk factors, including diabetes, dyslipidemia, CHD, and other cardiovascular conditions had stronger associations with midlife global cognitive decline in women compared to men,” the researchers wrote. “In addition, we also found that CHF and ever smoking had stronger associations with midlife language decline in men compared to women.”

“It is striking that even though men have a higher prevalence of cardiovascular risk factors and conditions in midlife, the impact of most of these conditions on cognition is stronger for women,” they observed.

These findings are not unprecedented, as earlier studies have suggested gender-specific associations between cardiovascular risk factors or conditions and later-life cognition. A 2008 study of 6,892 French people 65 or older found different risk profiles for cognitive impairment as well as dementia in men (stroke) and women (depressive symptoms and use of anticholinergic medication). A 2013 study in Italy of 5,632 participants ages 65-94 listed risks for men as heart failure, Parkinson’s disease, family history, depressive symptoms, and age, while for women they included age, depressive symptoms, glycemia, and BMI.

A 2020 study in a Hispanic population of 7,650 reported that women with midlife (ages 45-64) cardiovascular risk had stronger associations between risk and worse cognitive function.

A recent review of sex differences for cognitive impairment and dementia concluded that in addition to differences in cardiovascular disease risk factors (along with cardiovascular disease itself, and its treatment), hormonal and inflammatory differences, as well as other lifestyle factors and increased longevity, may account for the higher prevalence of impairment and dementia in women.

Limitations of the study included a homogenous sample, as the analysis was limited to predominantly White residents of Olmsted County, Minnesota, thus limiting generalizability. Also, small numbers for some cardiovascular conditions such as peripheral vascular disease and stroke led to their analysis as “other” in one group, and larger sample sizes are needed to determine their role in midlife cognitive decline in men and women. In addition, no information about the duration of cardiovascular conditions and risk factors was included in the analysis.

  1. Though the frequency of cardiovascular conditions and risk factors was higher in men than women in midlife, they differentially affected midlife cognitive decline, a cohort study found.

  2. In middle-aged patients, coronary heart disease (CHD) and other cardiovascular conditions were associated with global cognition decline, but only in women. Diabetes, dyslipidemia, and CHD were associated with language score decline, but again only in women. However, congestive heart failure was associated with language score decline only in men.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project.

Mielke is a consultant for Biogen and Brain Protection Company and on the editorial boards of Neurology and Alzheimer’s and Dementia.

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Topic ID: 82,130,730,358,364,446,5,6,8,914,130,361,38,192,916,925