Characterizing cerebral microhemorrhage associations in dementia subtypes in the UK Biobank

Abstract

AbstractBackgroundCerebral microbleeds (CMBs) are associated with neurodegenerative diseases (Charidimou, 2011) and have been identified as an adverse amyloid‐related imaging abnormality event (ARIA‐H) related to amyloid clearing medications (Sperling, 2011). Identifying risk factors for CMBs can help refine inclusion criteria for clinical trials and mitigate the risk of ARIA‐H. CMBs are readily detected on T2*‐GRE MRI sequences, including susceptibility weighted imaging (SWI) – a modality used to detect magnetic field distortions caused by paramagnetic products like iron (Haacke, 2004, Liu, 2017). We explore CMB associations with demographic, disease, and imaging markers in a subset of participants with varying dementia subtypes and complaints in the UK Biobank (Miller, 2016).MethodA total of 75 participants who had clinically diagnosed or self‐reported dementia and SWI imaging were selected; 4 participants were excluded due to extreme motion. We used MARS criteria (Gregoire, 2009) to identify CMBs on SWI and validated our findings using other sequences to exclude CMB ‘mimics’ (Figure 1A). The number, classification, and position of CMBs were recorded. Logistic regressions modeling the outcome of at least one ‘definite’ or ‘total’ (‘definite’ + ‘possible’) CMB were performed and effect sizes were calculated across hippocampal volume, white matter hyperintensity load (WMH), and global WM diffusion MRI (dMRI) microstructural measures.ResultParticipants were predominantly male (65%) with a mean age of 69.8 (± 7.1) years. 9 participants had at least one ‘definite’ CMB and 8 more had at least one ‘possible’ CMB for a ‘total’ of 17 individuals with CMBs. Individuals with CMB(s) were significantly older than those without. CMBs were mostly ‘strictly lobar’ for both definite (78%) and total (71%) classifications (Table 1). The presence of CMBs were found across a spectrum of dementia diagnoses (Figure 1B). Microstructural dMRI measures including global WM FA, MD, and ISOVF were significantly associated with presence of total CMBs (q<0.05) (Figure 2).ConclusionMeasures reflecting WM organization were sensitive to the pathophysiology of CMBs in those with dementia. Future work should investigate whether WM microstructure can predict the development of CMBs in those with dementia, particularly in individuals undergoing amyloid clearing treatments.