Considerations on accuracy, pattern and possible underlying factors of brain microbleed progression in older adults with absence or mild presence of vascular pathology

Abstract

Objective To analyse brain microbleed (BMB) progression, its possible underlying factors, and the influence of inter-observer differences, in older individuals with none or mild vascular pathology. Methods This study analysed magnetic resonance images, cognitive, demographic and laboratory data from all individuals from the Alzheimer's Disease (AD) Neuroimaging Initiative database who had the required sequences for identifying BMBs over three consecutive years at the time the database was accessed (January 2016). BMBs were assessed independently by two observers with similar levels of experience. Results A total of 291 patients were included in the study. The number of individuals with BMBs and the number of BMBs per individual slightly and nonsignificantly increased across three consecutive years (Y1: 55/291 [19%]; Y2: 61/291 [21%]; Y3: 66/291 [23%]) with 1-2 BMBs and (Y1: 11/291 [4%]; Y2: 12/291 [4%]; Y3: 14/291 [5%]) with ≥ 3 BMBs. Both observers identified a similar pattern of BMB prevalence and progression in each cognitive group (normal < early/late mild cognitive impairment (MCI) > AD patients) despite inter-observer differences (1.5 BMBs, 95% confidence interval -3.7, 6.2], κ=0.543), which were mainly in the cortex. Serum cholesterol was the main predictor of change in BMB count between time-points but did not predict overall progression. Conclusions Inter-observer differences are always present and it is difficult to ascertain their influence in the analysis of BMB progression, which was observed in cognitively normal and MCI individuals, but not in AD patients. This should be confirmed in further studies.

Keywords: Microbleeds; ageing; inter-observer differences; longitudinal; magnetic resonance imaging; progression.

Figure 1.

Schematic representation of the continuum of cognitive decline: from cognitively normal to dementia, as defined by the American Psychiatric Association, and the prevalence of brain microbleeds (BMBs) at its different stages. The colour version of this figure is available at: http://imr.sagepub.com.

Figure 2.

Baseline inter-observer variability and brain microbleed (BMB) prevalence. (a) Bland-Altman plot for BMB count. The difference in BMB count between observers is plotted against the mean BMB count for 150 patients. It increased with the increase of the mean number of BMB counted by both observers. The mean difference of BMB count between observers is 1.47 (95% confidence interval [–3.7, 6.2], suggesting a bias towards Observer 2 reporting a higher count. Larger circles in the graph represent greater numbers of observer comparisons for these data points. (b) Percentage of patients with BMBs in each cognitive group reported by each observer in the same subsample of 150 patients. CN, cognitively normal; EMCI, early mild cognitive impairment; LMCI, late mild cognitive impairment; AD, Alzheimer’s Disease. The colour version of this figure is available at: http://imr.sagepub.com.

Figure 3.

Longitudinal inter-observer differences per cognitive group in 20 patients. Each patient is represented by a different colour and the patient colours correspond for both observers. *Representative of more than one patient. Brain microbleed (BMB) count refers to the number of BMBs that each observer counted on each scan. CN, cognitively normal; EMCI, early mild cognitive impairment; LMCI, late mild cognitive impairment. The colour version of this figure is available at: http://imr.sagepub.com.

Figure 4.

Factors that affected inter-observer variability as seen on magnetic resonance imaging T2*-weighted gradient-recalled echo images (arrows): (a) vessel calcifications; (b) basal ganglia mineralization; (c) reduced cortical thickness.