Midlife Cognitive Decline Linked to Cardio Factors in Women

Cognitive decline in midlife had stronger ties to cardiovascular conditions and risks for women than men, a longitudinal study showed.

Coronary heart disease, for example, was linked to a more than two-fold greater decline in global cognitive test scores for women (P<0.05), reported Michelle Mielke, PhD, of the Mayo Clinic in Rochester, Minnesota, and co-authors.

Dyslipidemia, coronary heart disease, and diabetes were associated with declines in language scores, but only in women, they wrote in Neurology. Congestive heart failure, on the other hand, was associated with language score declines, but only in men (all P<0.05).

“Most studies examining cardiovascular conditions and risk factors in relation to cognition have either measured both in late life — roughly after age 70 — or have examined midlife cardiovascular factors in relation to risk of late-life cognitive impairment or dementia,” Mielke told MedPage Today.

“Recently, a few studies have shown that cardiovascular factors in midlife are associated with midlife cognition,” she added. “However, these studies have generally not examined sex differences.”

“It is well known that men have a higher frequency of cardiovascular conditions and risk factors in midlife; the prevalence for women increases after menopause and women eventually catch up to men in later life,” Mielke said.

“Despite the higher prevalence of these conditions and risk factors in men, we found that women who had the risk factors and conditions had more cognitive decline in midlife,” she noted. “Thus, the cardiovascular conditions and risk factors in midlife are more detrimental to women’s cognitive health.”

The findings were based on 1,857 dementia-free participants in the Mayo Clinic Study on Aging who were 50 to 69 years old at their baseline visit from February 2012 to February 2020. Mean follow-up time was 3 years.

Cardiovascular conditions and risk factors were culled from medical records. Conditions included coronary heart disease, arrhythmias, congestive heart failure, peripheral vascular disease, and stroke, while risk factors included hypertension, diabetes, dyslipidemia, smoking, BMI, and obesity.

Only 33 people experienced a stroke and 43 had peripheral vascular disease; these were grouped together as “other cardiovascular conditions” in analyses. Multivariable models adjusted for demographics, APOE genotype, depression, and other medical conditions.

Participants had neurologic evaluations and neuropsychological testing every 15 months, including nine tests to calculate global cognitive and domain-specific (memory, language, executive function, and visuospatial skills) z scores.

Overall, 78.9% of participants had at least one cardiovascular condition or risk factor; the proportion was higher for men (83.4%) than women (74.5%; P<0.0001). Men also had a higher frequency of each individual cardiovascular condition or risk factor.

Overall, baseline hypertension, diabetes, dyslipidemia, coronary heart disease, other cardiovascular conditions, and smoking were associated with greater declines in global cognitive z scores.

Multiple conditions were also associated with declines in domain-specific z scores. Diabetes, coronary heart disease, other cardiovascular conditions, and smoking at baseline were linked to significantly greater declines in memory, language, and attention domains. Hypertension was tied to greater declines in language and attention, while congestive heart failure was associated with a greater decline in memory.

In sensitivity analyses, the researchers excluded participants with prevalent or incident mild cognitive impairment or a history of stroke and found results were similar to the primary analyses.

“Understanding sex differences in the development and progression of cognitive decline and dementia will improve treatment and prevention strategies for both women and men,” Mielke noted.

“Although it is important to treat cardiovascular conditions and risk factors for both women and men, the results suggest that women with these factors in midlife may be more susceptible to cognitive decline and should be monitored more closely,” she added.

The study was limited to participants in Olmsted County, Minnesota, and results may not apply to other populations, Mielke and co-authors acknowledged. The researchers also did not have information about the duration of all cardiovascular conditions or risk factors and did not incorporate that data into the study.