Marked Cognitive Decline in Husbands After a Spouse’s CVD Event?

Incident cardiovascular disease (CVD) in one spouse was followed by the other developing dementia more often than expected in a large Japanese cohort study.

In the study’s predominantly male cohort of seniors, the dementia diagnosis incidence rate ratio was 1.32 (95% CI 1.10-1.57) over a median 24 months of follow-up after a spouse’s CVD event compared with those whose spouse had no CVD event, reported Kosuke Inoue, MD, PhD, of Kyoto University in Japan, and colleagues in JAMA Neurology.

“This is one of the first and largest studies investigating potential interpersonal pathways associated with elevated dementia risk,” Inoue’s group wrote. “Identifying how one spouse’s health is associated with the other spouse’s health can help direct timely, needed resources for people at risk of dementia.”

Without a clear explanation for their finding, the authors pointed to the possibility that a traumatic occurrence such as incident CVD or a death may affect the spouse’s cognitive function or that a change in a spouse’s lifestyle may have taken place after the index person’s CVD event.

It is also possible that the index spouse had some baseline cognitive impairment that only became more apparent with the added stress and high-level needs of caring for the spouse with CVD, according to epidemiologist Michelle Mielke, PhD, of Wake Forest University School of Medicine in Winston-Salem, North Carolina, who was not involved with the study.

In any case, Ambar Kulshreshtha, MD, PhD, a family physician at Emory Healthcare in Atlanta, agreed with directing attention and resources to families of CVD patients based on the Japanese data.

“This finding is particularly important for primary care clinicians who often provide continuity of care to multiple members of the same family and often spouses. Following these stressful life events, primary care clinicians can provide access to resources such as behavioral health referrals to help spouses and family members with better coping strategies and emphasize self-care,” he commented in an email. “Timely screening, controlling risk factors, and advance care planning should be addressed at every opportunity.”

Notably, the people compared in the study were by and large husbands with or without spouses with CVD — with fewer than 4% of the index patients being women. “Because caregiving burdens and social isolation could vary by sex, further research with enough female samples is needed to establish the sex-specific association,” the investigators acknowledged.

Peter Vitaliano, MS, PhD, a stress researcher at the University of Washington in Seattle, emphasized the male dominance of the study, noting that “relationships between CVD factors and dementia may differ for men and women because of social and biochemical factors.”

“It should be noted that, although the last several years have seen an increased interest in relationships of caregiver cognition to care-recipient diseases, research in this area has been going on since 2003,” said Vitaliano. “At that time, our group showed that spouse caregivers of persons with Alzheimer’s disease [AD] had worse short-term memory than spouses who were not caregivers and not married to someone with AD. We also showed that higher levels of depression and sleep problems in caregivers helped to explain this difference.”

He told MedPage Today that later longitudinal analysis suggested a role played by higher glucose and insulin in caregivers than non-caregivers. “These are all risk factors for dementia,” as well as coronary heart disease, he stressed.

Inoue’s cohort study included individuals 65 and older in the Japan Health Insurance Association insurance program who were dementia-free when their spouse experienced a CVD event from 2016 to 2022. Investigators performed a target trial emulation analysis to try to adjust for confounding; each index person was matched to a comparator whose spouse had no CVD event during the study window.

After matching, there were 93,396 index individuals included in the analysis (mean age 68.8 years, 96.2% men).

There was no information provided about the spouses’ activities or rates of depression, anger, and anxiety relative to the spouses of people who did not have CVD.

Inoue’s group acknowledged that study limitations included short follow-up, potential for uncontrolled confounding, and lack of important socioeconomic variables in the database.

Additionally, Vitaliano cautioned that the study likely did not fully control for education, and it was unclear if any of the women were taking any hormone replacement therapy linked to CVD and dementia.

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