Clinical correlates of cerebral microbleeds are diminished in individuals with traumatic brain injury

Abstract

Introduction

Cerebral microbleeds (CMB) are predictive of increased risk of dementia and stroke. Although commonly regarded as vascular markers, CMB can also stem from non-vascular aetiologies like head injuries or traumatic brain injury (TBI), although these are often overlooked. Therefore, this study examines CMB in relation to TBI, and their differential causes (i.e., risk factors) and consequences (i.e., clinical outcomes).

Methods

In 605 healthy middle-aged adults (aged 40-59), CMB were rated on 3T susceptibility weighted imaging (SWI) MRI. TBI was assessed using the Brain Injury Screening Questionnaire (BISQ). TBI+ was defined as at least one blow to the head resulting in loss of consciousness (36.0%; n=217). Memory was assessed using the COGNITO battery. Interaction analyses examined TBI*CMB interactions on hypertension, gait, and memory. Dominance analysis examined the relative contribution of TBI and vascular risk factors on predicting gait disturbances and memory. All models adjusted for sex, age, education, and study site.

Results

TBI was related to higher CMB count (t=2.06, p=.039), and were more common in males (48.3%) than females (28.0%) (χ2=28.91, p<.001). Number of TBI events related to poorer memory (t=-2.62, p=.009) and gait disturbances (t=3.54, p<.001). Interaction analyses demonstrated that hypertension (t=-2.26, p=.024), memory (t=2.70, p=.007) and gait (t=-2.29, p=.023) were less closely related to CMB in individuals with greater number of TBI events, relative to those with fewer TBIs. Regionally, these interactions were significant for lobar CMB, but not deep subcortical CMB. Within the TBI+ group, dominance analysis demonstrated that number of TBI events outperformed vascular risk factors in predicting gait disturbances (Contribution to R2: TBI=52.9%, vascular risk=32.6%) and memory (TBI=28.7%, vascular risk=1.2%).

Discussion

CMB appeared to differ aetiologically and clinically in those with and without TBI. In individuals with TBI, TBI itself was the dominant driver of clinical deficits. While vascular CMB may appear more detrimental than traumatic CMB at baseline, longitudinal analysis is required to determine how traumatic CMB differ in clinical trajectory and downstream pathologies. This study highlights the importance of differentiating between CMB of vascular origins vs. TBI in both research and clinically to aid prognosis and treatment decisions.