Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy

Abstract

Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical thickness was measured using surface based methods. Presence of restricted multiple lobar CMBs were independently associated with cortical thinning across the entire cortical regions while presence of CSS was independently associated with cortical thinning primarily in the bilateral frontal region. Presence of restricted multiple lobar CMBs was associated with impairment in all cognitive domains such as attention, language, visuospatial, memory and frontal executive functions while presence of CSS was associated with attention and frontal dysfunction. The relationships of restricted multiple lobar CMBs or CSS with cognitive impairment were partially mediated by thinning in the corresponding cortical regions. Our findings suggested that restricted multiple lobar CMBs and CSS affect distinctive clinical features, providing new insights into potential mechanisms in CAA.

Figure 1

Trend analyses of clinical characteristics. Figure showed a significant trend of older age (a), a higher frequency of APOE ε4 (b), poorer cognitive status (c), and more severe deep (d) and periventricular (e) white matter hyperintensities among non-CAA, possible CAA, and probable CAA groups in order. CAA cerebral amyloid angiopathy.

Figure 2

Topography of cortical thinning. Multiple lobar CMBs were associated with cortical thinning in bilateral medial and lateral frontal, medial and lateral temporal, lateral parietal, and occipital regions. (a) CSS was associated with cortical thinning in bilateral medial and lateral frontal, medial temporal and occipital and right lateral temporal regions. (b) Multiple lobar CMBs, and CSS were entered in a general linear model. Age, sex, education, intracranial volume, white matter hyperintensities, and another haemorrhagic marker were entered as covariates. CMBs cerebral microbleeds; CSS cortical superficial siderosis.

Figure 3

Path analyses for cognition. Multiple lobar CMBs and/or CSS were associated with attention (a), language (b), visuospatial (c), memory (d), and frontal executive (e) dysfunctions partially mediated by cortical thickness of corresponding area, respectively. The numbers on the paths are standardized coefficients which showed statistical significances. Cortical thickness was entered as a mediator variable for cognitive function. Multiple lobar CMBs, and CSS were entered as predictors. Age, sex, education, and white matter hyperintensities entered as covariates. The numbers on the paths are standardized coefficients. Direct paths that were statistically significant were reported. CMBs cerebral microbleeds; CSS cortical superficial siderosis.