Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.
Analyses of almost 1400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.
Dr Michelle Mielke
“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.
The findings were published online January 5 in Neurology.
Assessing Sex Differences
Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Mielke noted.
However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.
They assessed 1857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.
Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs 74.5%; P < .0001).
Frequency of each individual CV condition or risk factor was also higher in men than women; and they had more years of education and higher BMI, but took fewer medications.
Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.
The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
Multiple Cognitive Domains
Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.
They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.
Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.
Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.
As some participants didn’t have a follow-up visit, the current analysis included 1394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.
Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).
CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.
Mielke cautioned about reading too much into the language results for women.
“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
“Treat Aggressively and Right Away”
The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Mielke.
“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.
As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Mielke said she wants to “move beyond” just looking at hormones.
She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.
“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Miekle said.
Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.
Mielke stressed the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.
In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Mielke.
“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”
Study limitations cited include that its sample was limited to Olmsted County, Minnesota ― so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
Helpful for Tailoring Interventions?
Commenting on the study for Medscape Medical News, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.
“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Finney, who was not involved with the research.
Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”
Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.
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 is on the editorial boards of Neurology and Alzheimer’s and Dementia. Finney has reported no relevant financial relationships.
Neurology. Published online January 5, 2022. Abstract
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