Assessment of Cognitive Function via Biomarkers in Japanese Patients With Chronic Heart Failure Treated With Angiotensin-Receptor-Neprilysin Inhibitor

Abstract

Background: Angiotensin-receptor-neprilysin inhibitors (ARNIs) improve outcomes in patients with chronic heart failure (CHF). However, neprilysin is a major amyloid beta (Aβ)-degrading enzyme in the brain and although previous studies suggest that ARNI use does not induce neurocognitive dysfunction in CHF patients, data in Japanese patients are limited.

Methods and Results: This single-center, prospective, observational study enrolled 15 CHF patients: 6 who were being treated with ARNI (ARNI) and 9 who were not (non-ARNI). Cognitive assessments and blood biomarkers were evaluated at baseline and 1-year follow-up. Participants from the Parkinson’s and Alzheimer’s Disease Dimensional Neuroimaging Initiative cohort, comprising 7 patients with cerebral Aβ deposition (Aβ-positive) and 7 patients without deposition (Aβ-negative), were used for comparison. Despite the small sample size, significant differences in the Japanese version of Montreal Cognitive Assessment score and tau phosphorylated at threonine 181 level were observed between the Aβ-negative and Aβ-positive groups. In contrast, no significant difference in cognitive function or blood biomarkers were found between the non-ARNI and ARNI groups at baseline or after 1 year of follow-up.

Conclusions: In this pilot-scale study, ARNI use was not associated with cognitive impairment or elevated blood biomarkers related to cognitive dysfunction in Japanese patients with CHF. Due to the limited sample size and follow-up, further validation in larger, long-term trials is warranted.