Plasma neurofilament light is associated with cognitive impairment in patients hospitalized for heart failure
A Yaghoubi, J Molvin, S Janelidze, A Jujic, O Hansson, M MagnussonAbstract
Background
Cognitive impairment (CI) is highly prevalent in patients with heart failure (HF) and associated with increased mortality and morbidity. Despite its clinical impact, the underlying pathophysiological mechanisms remain incompletely understood, and reliable biomarkers for early risk stratification are lacking. Neurofilament light (NfL) and Plasma Phosphorylated Tau-217 (p-tau217) are two promising biomarkers that have been shown to have predictive value for CI in patients with Alzheimer’s disease and in the general population. However, data on their predictive ability of CI in HF patients is scarce.
Aims
To investigate whether p-tau217 and NfL are associated with cognitive impairment in HF patients.
Method
Among 491 patients hospitalized for HF, 304 patients were assessed with Montreal Cognitive Assessment (MoCA), which measures global cognitive function across several domains and Trailmaking test A (TMT-A), which primarily assesses processing speed, visual attention, and psychomotor speed and 301 patients were assessed with using Symbol digit modalities test (SDMT), which evaluates information processing speed, attention, and working memory. Plasma concentrations of NfL and p-tau217 were analyzed in relation to cognitive test performance using multivariable linear regression models, adjusted for age, sex, body mass index, prior stroke, and educational level.
Results
The median age was 76 years (IQR 67-83) and 31 % were female. Median scores for cognitive tests were: MoCA: 26 points (IQR 23-27), SDMT: 25 points (IQR 19-32) and TMT-A: 55 seconds (IQR 39,5 - 75). Both NfL and p-tau217 showed a significant association to worse cognitive performance on SDMT, ß = -2.18 (95% CI −3.71 to −0.66) and ß -2.60 (95% CI −4.66 to −0.53), respectively, in the fully adjusted linear regression model. For TMT-A, NfL showed a significant association to worse cognitive performance: β = 0.086 (95% CI 0.013–0.159), with p-tau217 showing no significant association after adjustment. Neither biomarker showed any significant association to cognitive performance on MoCA in the fully adjusted models.
Conclusion
In patients hospitalized for HF, higher levels of NfL showed a significant association to declining cognitive performance as assessed by SDMT and TMT-A, whilst p-tau217 only showed a significant association to declining cognitive performance when assessing it using SDMT. These findings suggest that NfL may serve as a promising biomarker for identifying HF patients at increased risk of cognitive decline in specifically speed, attention, and cognitive flexibility, warranting further longitudinal studies.