Cerebral microbleeds on susceptibility-weighted imaging, cognitive domains, and serum neurofilament light chain in adults with hypertension

Abstract

Hypertension is associated with cognitive impairment, and cerebral microbleeds (CMBs) may reflect hemorrhagic small-vessel injury. We examined whether CMB burden and location were associated with global and domain-specific cognition in adults with primary hypertension and whether serum neurofilament light chain (sNFL) provided additional discrimination for identifying mild cognitive impairment (MCI) beyond CMB count. In this single-center cross-sectional study, 173 hospitalized adults aged 31–95 years with a pre-existing diagnosis of primary hypertension underwent brain magnetic resonance imaging (MRI) with susceptibility-weighted imaging, the Montreal Cognitive Assessment (MoCA), and sNFL measurement by enzyme-linked immunosorbent assay (ELISA). Six MoCA-derived cognitive domain z-scores were calculated. CMB burden was categorized as 0, 1–4, or ≥5 lesions. Multivariable logistic and linear regression models were adjusted for age, sex, education, systolic blood pressure, diabetes, and prior stroke. Sensitivity analyses additionally adjusted for other cerebral small vessel disease markers, modeled the CMB count as a continuous variable, and excluded participants with prior stroke. CMBs were detected in 82 patients (47.4%) and MCI in 83 patients (48.0%). Greater CMB burden was independently associated with MCI (adjusted odds ratio (OR): 4.53, 95% CI 1.95–10.55). After covariate adjustment and false-discovery-rate correction, greater CMB burden was associated with lower executive function, orientation, attention, and visuospatial function scores, but not with memory or language. Cognitive domain scores did not differ according to CMB location. CMB count and sNFL were inversely correlated with cognitive performance. The areas under the curve for identifying MCI were 0.683 for CMB count, 0.794 for sNFL, and 0.792 for the combined model. The combined model had a larger area under the curve than CMB count alone ( p  < 0.001) but did not differ from sNFL alone ( p  = 0.768). In adults with primary hypertension, greater CMB burden was associated with MCI and selected cognitive domains, whereas cognitive performance did not differ according to CMB location. sNFL had a numerically higher area under the curve than CMB count, and adding CMB count did not improve discrimination beyond sNFL. These findings may help characterize cognitive vulnerability in hypertension; therefore, prospective validation is required before clinical application.