Strategic corpus callosum lesions are associated with worse cognitive performance in cerebral amyloid angiopathy

Abstract

AbstractBackgroundCerebral amyloid angiopathy (CAA) is highly prevalent in Alzheimer’s disease (AD) and is associated with hemorrhagic and ischemic brain lesions. CAA is increasingly recognized as an important independent cause of cognitive impairment. However, the mechanisms underlying cognitive impairment in these patients are poorly understood. We hypothesized that lesions in the corpus callosum (CC), because of their strategic location, are associated with widespread reductions in microstructural white matter integrity and worse cognitive performance, specifically in the domains of attention/information processing speed and executive functioning.Method57 individuals meeting the modified Boston criteria for probable CAA underwent 3T MRI, including a DTI scan, and neuropsychological testing. Microstructural white matter integrity was quantified by means of fractional anisotropy and mean diffusivity. Test scores on individual neuropsychological tests were converted into Z‐scores and averaged into the following cognitive domains: memory, attention/information processing speed, language, executive functioning, and visuospatial processing. CC lesions were defined as hemorrhagic (microbleeds or larger bleeds) and ischemic (microinfarcts, lacunar infarcts, and FLAIR hyperintensities). Associations between CC lesion presence, microstructural white matter integrity, and cognitive performance were examined with multiple regression models, corrected for age, sex, education (when cognition was the dependent variable), and history of large ICH. False discovery rate corrections for multiple comparisons were applied.ResultDemographic and imaging characteristics of cases with and without CC lesions are outlined in table 1. Sixteen cases (28%) had one or two CC lesions (n=18 lesions). Most lesions were located in the splenium (n=8), followed by the genu (n=7) and the midbody (n=3) of the CC. In multivariate regression models, presence of CC lesions was associated with reduced microstructural white matter integrity on DTI within the CC and in the total white matter. Interestingly, cases with CC lesions performed significantly worse on the domains of attention/information processing speed, and executive functioning compared to those without CC lesions, but no differences were found for the other domains (table 2).ConclusionBecause of their strategic location, focal CC lesions may significantly contribute to cognitive impairment in CAA, potentially through their negative impact on the microstructural white matter integrity beyond the lesion core (i.e., Wallerian degeneration).