Cerebral Microhemorrhage at MRI in Mild Cognitive Impairment and Early Alzheimer Disease: Association with Tau and Amyloid β at PET Imaging.

Abstract

Background Growing evidence indicates an association between cerebral microhemorrhages (MHs) and amyloid β accumulation in Alzheimer disease (AD), but to the knowledge of the authors the association with tau burden is unknown. Purpose To investigate the association between cerebral MH load and tau pathologic structure measured in healthy older individuals and individuals along the AD spectrum, stratified by using the A (amyloid β)/T (tau)/N (neurodegeneration) biomarker classification system. Materials and methods In this prospective cohort study, participants from the AD Neuroimaging Initiative were included (healthy control participants, participants with mild cognitive impairment, and participants with AD dementia; data from October 2005 to January 2019). T2*-weighted gradient-echo MRI was performed to quantify MH, fluorine 18 (¹⁸F) flortaucipir (AV-1451) PET was performed to quantify tau, and ¹⁸F-florbetaben/¹⁸F- florbetapir (AV45) PET was performed to quantify amyloid β to study associations of MH with regional and global tau and amyloid β load. Associations with cerebrospinal fluid (CSF) biomarkers (amyloid β1-42, total tau, phosphorylated tau 181) were also assessed. Analysis of covariance and Spearman rank correlation test for cross-sectional analysis and Wilcoxon signed rank test for longitudinal analyses were used, controlling for multiple comparisons (Bonferroni significance threshold, <i>P</i> < .008). Results Evaluated were 343 participants (mean age, 75 years ± 7; 186 women), including 205 participants who were A-TN- (mean age, 73 years ± 7; 115 women), 80 participants who were A+TN- (mean age, 76 years ± 7; 38 women), and 58 participants who were A+TN+ (mean age, 77 ± 8; 34 women). MH count was associated with global (Spearman ρ = 0.27; <i>P</i> = .004) and frontal (ρ = 0.27; <i>P</i> = .005) amyloid β load and global tau load (ρ = 0.31; <i>P</i> = .001). In a longitudinal analysis, MH count increased significantly over approximately 5 years in the entire cohort (T-1, 81 [range, 0-6 participants]; T0, 214 [range, 0-58 participants]; <i>P</i> < .001), in A+TN+ (T-1, 20 [range, 0-5 participants]; T0, 119 [range, 1-58 participants]; <i>P</i> < .001), A+TN- (T-1, 31 [range, 0-6 participants]; T0, 43 [range, 0-8 participants]; <i>P</i> = .03), and A-TN- (T-1, 30 [range, 0-4 participants]; T0, 52 [range, 0-6 participants]; <i>P</i> = .007). A higher MH count was associated with higher future global (ρ = 0.29; <i>P</i> = .008) and parietal (ρ = 0.31; <i>P</i> = .005) amyloid β and parietal tau load (ρ = 0.31; <i>P</i> = .005). Conclusion Cerebral microhemorrhage load is associated spatially with tau accumulation, both cross-sectionally and longitudinally. © RSNA, 2020 <i>Online supplemental material is available for this article.</i>