Dementia, Not Depression, Drives Poor Outcomes in Peripheral Artery Disease

Peripheral arterial disease, the narrowing of the arteries that supply blood to the legs, is one of the most common circulatory conditions of aging, affecting hundreds of millions of people worldwide. Cardiologists have long known that mental health conditions frequently accompany the disease, but a sweeping new analysis of German health insurance claims suggests that the field has been lumping together conditions that behave very differently. In a nationwide cohort study published in Clinical Research in Cardiology, researchers led by Esra Tokur Sonuvar of Leipzig University and Eva Freisinger of University Hospital Leipzig examined nearly one hundred thousand patients hospitalized for peripheral arterial disease and found that nearly half carried a diagnosis of depression, anxiety, or dementia. Yet when the team teased these conditions apart, only one of them emerged as a powerful and independent driver of death and limb loss: dementia.

The study drew on claims data from AOK – Die Gesundheitskasse, one of Germany’s largest statutory health insurers, allowing the investigators to identify 99,415 patients hospitalized for peripheral arterial disease between January 1, 2019 and December 31, 2020. This scale matters. Most previous studies of mental health in vascular disease have been small, single-center efforts that often conflated depression, anxiety, and cognitive impairment into a single category of psychological comorbidity. By contrast, the German dataset offered the statistical power to compare these disorders head to head, using multivariable-adjusted analyses and Cox regression models to account for age, sex, disease severity, and other cardiovascular risk factors.

The headline finding is striking in its simplicity: 47 percent of patients hospitalized for peripheral arterial disease had at least one of the three mental disorders. That figure alone should reshape how vascular teams think about their patient population. Patients with these conditions were more frequently female, presented with more advanced stages of arterial disease, and carried a heavier overall cardiovascular risk profile. In other words, the sickest patients with the most compromised circulation were also the ones most likely to be living with a mental health diagnosis, a convergence that sets the stage for the treatment disparities the study went on to document.

When the researchers disaggregated the three conditions, the picture became far more nuanced than the conventional wisdom suggests. Dementia stood out as the condition associated with the most pronounced disparities in care. Patients with dementia underwent revascularization, the procedures that restore blood flow to blocked leg arteries, at substantially lower rates than their peers. They also received statin therapy, the cornerstone guideline-recommended cholesterol-lowering treatment for atherosclerotic disease, far less often, despite presenting with more advanced disease at the time of hospitalization. This pattern of undertreatment in the face of greater need represents what the authors describe as an important and underrecognized gap in vascular care.

The prognostic consequences of dementia were equally dramatic. In the Cox regression models, dementia emerged as a strong independent predictor of all-cause mortality, with hazard ratios ranging from 1.57 to 1.62, meaning that patients with dementia faced a roughly 60 percent higher risk of death during follow-up compared with otherwise similar patients. Dementia also predicted the composite outcome of amputation and/or death, with hazard ratios between 1.49 and 1.56, and both associations were highly statistically significant. For a condition that is often treated as a background characteristic rather than a clinical variable, these numbers place dementia firmly in the category of major prognostic factors in peripheral arterial disease.

Depression, by contrast, told a quieter story. Although depression was the most prevalent of the three conditions and has been the focus of most prior research linking mental health to vascular outcomes, its association with adverse outcomes in this cohort was only modest after full statistical adjustment. Anxiety disorders fared even worse as prognostic markers, showing no consistent association with increased risk once the models accounted for other clinical variables. The authors conclude that mental disorders in peripheral arterial disease are not prognostically homogeneous, a phrase that carries real weight for trial designers, guideline writers, and clinicians who have traditionally bundled these conditions together under a single comorbidity flag.

Why might dementia exert such a disproportionate influence? The study itself points toward a combination of biological and systems-level mechanisms. On the biological side, dementia and peripheral arterial disease share deep vascular roots: atherosclerosis, endothelial dysfunction, and chronic inflammation injure both the brain and the limbs, and prior nationwide studies have shown that the risk of dementia differs across cardiovascular diseases and dementia subtypes. On the systems side, cognitive impairment complicates every step of vascular care. Patients with dementia may report claudication symptoms late or not at all, may struggle to adhere to complex medication regimens including statins and antiplatelet agents, and may be deemed poor candidates for revascularization by clinicians weighing procedural risk against limited expected benefit. Previous work in vascular surgery populations has documented that cognitive impairment is common and frequently undiagnosed in older patients undergoing vascular procedures, and that patients with dementia undergoing major limb amputation have particularly poor outcomes.

The treatment disparities documented in the study echo a pattern seen in other cardiovascular fields. Research on stroke care has shown that dementia is associated with poorer quality of care and worse outcomes after stroke, and the new findings suggest that a similar dynamic operates in the peripheral circulation. Whether the lower rates of revascularization and statin therapy in patients with dementia reflect explicit clinical judgment, implicit bias, communication barriers, or patient and family preferences cannot be determined from claims data alone. But the result is a vulnerable population that receives less of the therapy that guidelines recommend for everyone with atherosclerotic disease, while simultaneously bearing the highest risk of dying or losing a limb.

The study’s methodology deserves attention as well. Claims data offer unmatched scale and the ability to capture real-world treatment patterns across an entire country, but they also carry limitations inherent to administrative records. Diagnoses depend on coding practices, the severity of dementia and depression cannot be graded, and over-the-counter medications and care delivered outside the hospital may escape detection. The authors also note that the data are held by the Wissenschaftliches Institut der AOK in Berlin and are not publicly available, with access governed by contractual and data protection regulations. The work was funded as part of the LINCARE project by the Innovation Fund of the Federal Joint Committee, the German body that steers innovation in statutory health care.

For clinicians, the practical message is that screening for cognitive impairment should become as routine in vascular clinics as measuring the ankle-brachial index. For researchers, the findings argue for disaggregating mental health comorbidities in future trials and registries rather than collapsing them into a single variable. And for health systems, the study highlights a population in which coordinated care, involving vascular specialists, geriatricians, psychiatrists, and primary care physicians working together, could plausibly change outcomes that are currently among the worst in cardiovascular medicine. As the authors put it, dementia identifies a particularly vulnerable and undertreated peripheral arterial disease population, and recognizing that distinction is the first step toward closing a gap in care that has remained invisible for far too long.

Subject of Research: The differential impact of depression, anxiety, and dementia on prognosis and treatment patterns in patients hospitalized for peripheral arterial disease

Article Title: Not all mental disorders matter equally in peripheral arterial disease: Dementia drives prognosis and care disparities

Article References: Not all mental disorders matter equally in peripheral arterial disease: Dementia drives prognosis and care disparities. (n.d.). https://doi.org/10.1007/s00392-026-03027-w

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03027-w

Keywords: peripheral arterial disease, dementia, depression, anxiety disorders, revascularization, statin therapy, amputation, mortality, claims data, health care disparities, cardiovascular risk, vascular care