Cerebral microbleeds in patients with mild cognitive impairment and small vessel disease: The Vascular Mild Cognitive Impairment (VMCI)-Tuscany study

Highlights

• Cerebral microbleeds (CMBs) were assessed in small vessel disease MCI patients.

• Microbleed Anatomical Rating Scale reliable for assessment of CMBs in this cohort

• CMBs load is an independent contributor to cognitive impairment.

• The presence of CMBs is associated with specific cognitive domains.

Abstract

Background and objectives

Cerebral microbleeds (CMBs) are a neuroimaging expression of small vessel disease (SVD). We investigated in a cohort of SVD patients with mild cognitive impairment (MCI): 1) the reliability of the Microbleed Anatomical Rating Scale (MARS); 2) the burden and location of CMBs and their association with cognitive performances, independent of other clinical and neuroimaging features.

Methods

Patients underwent clinical, neuropsychological (4 cognitive domains), and MRI assessments. CMBs were assessed by three raters.

Results

Out of the 152 patients (57.2% males; mean age ± SD: 75.5 ± 6.7 years) with gradient-echo (GRE) sequences, 41 (27%) had at least one CMB. Inter-rater agreement for number and location of CMBs ranged from good to very good [multi-rater Fleiss kappa (95%CI): 0.70–0.95]. Lacunar infarcts and some clinical variables (e.g., hypertension and physical activity) were associated with CMBs in specific regions. Total number of CMBs and of those in deep and lobar regions were associated with attention/executive and fluency domains.

Discussion

MARS is a reliable instrument to assess CMBs in SVD patients with MCI. Nearly one third of these patients had at least one CMB. Total CMBs burden was associated with attention/executive functions and fluency domains impairment, lacunar infarcts, and with some potentially modifiable risk factors.

Introduction

Cerebral microbleeds (CMBs) are one of the neuroimaging markers of small vessel disease (SVD) [1], [2]. CMBs are small chronic brain hemorrhages, most likely caused by structural abnormalities of the cerebral small vessels [3]. They are radiologically defined lesions on magnetic resonance imaging (MRI) gradient-echo (GRE) T2* weighted or susceptibility-weighted images (SWI), corresponding histopathologically to focal hemosiderin depositions surrounding small vessels [3], [4]. In recent years, the use of the above-mentioned MRI sequences has led to an increased interest in CMBs, which are now increasingly recognized in different populations, might have a role in the clinical course of SVD and potentially prognostic and therapeutic consequences [5], [6], [7].

CMBs are frequently observed in community dwelling elderly subjects and their prevalence gradually increases with age [8], [9], being around 36% in patients > 80 years [8]. This prevalence further upsurges in the setting of stroke [10], [11], [12], [13] and in some conditions, such as cognitive impairment [14], while patients with no risk factors or known vascular disease may be at lower risk of CMBs [15]. The reported prevalence of CMBs in patients affected by mild cognitive impairment (MCI) ranges from 20 to 44%, also according to different MRI sequences used [16]. The prevalence is even higher in progressive MCI patients compared to stable MCI [17]. Evidence from both clinic-pathological correlations and large epidemiological studies supports differing topographic patterns of CMBs distribution according to their etiology. CMBs in deep or infratentorial regions are hypothesized to be associated with hypertensive microangiopathy, while those in lobar regions may be due to cerebral amyloid angiopathy [3], [18], [19], [20]. Originally thought to be asymptomatic markers of SVD, CMBs have been now considered as relevant contributors to cognitive impairment, both in general elderly populations [21], [22], [23] and in patients affected by SVD [24], [25], although their specific impact on cognition differs in different cohorts [21]. Furthermore, the topographic distribution of CMBs may have specific associations with certain cognitive domains [26], [27].

The reliable rating of CMBs presence, burden (number) and anatomical distribution in the brain using standardized rating scales is an essential prerequisite to investigate their clinical significance. This was also recently recommended in the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) position paper [2], according to which these lesions have to be recorded in terms of number and distribution applying one of the two available standardized visual scores [2], [3], [28], [29]. The Microbleed Anatomical Rating Scale (MARS) has reported good feasibility [28], [30].

So far, few studies exist that are focused on CMBs and their clinical significance in patients affected by MCI and SVD. The aims of our study were to evaluate in the Vascular Mild Cognitive Impairment (VMCI)-Tuscany Study cohort: 1) the feasibility and reliability of MARS; 2) the presence, number, topographic distribution of CMBs and their possible associations with cognitive performances, independent of their possible associations with other clinical and neuroimaging features.