Cerebral amyloid angiopathy frequency at baseline and after 4 years of follow‐up in the INSIGHT‐preAD study

Abstract

AbstractBackgroundCerebral amyloid angiopathy (CAA) diagnostic is of special interest due to its association with cognitive impairment, Alzheimer disease (AD) and Amyloid‐Related Imaging Abnormalities (ARIA) in trials with anti‐amyloid immunotherapies. We aimed to assess the frequency of CAA diagnosis and associated lesions in subjects with cognitive complaint and normal cognition enrolled in the INSIGHT‐preAD study.MethodCognitively normal elderly with memory complaint included in the INSIGHT‐preAD study were assessed with multimodal explorations for 5 years follow‐up. 3T MRI‐scans were performed at baseline and during follow‐up at 2 and 4 years. Lobar cerebral microbleeds (CMB), cortical superficial siderosis (CSS), enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were rated according to validated scales and guidelines. Boston criteria V2.0 were applied to diagnose possible and probable CAA.ResultAmong the 318 subjects (median [Q1, Q3] age: 76.4 [74.1, 78.5] years, 201 (63.2%) women) enrolled at baseline, 41 (12.9%) had at least one lobar CMB, 4 (1.3%) CSS, 68 (21.7%) severe EPVS in the centrum semi‐ovale and 245 (77%) WMH with a spot pattern ≥10. The median FAZEKAS score was 2.0 [1.0, 2.0]. At baseline, 251 (78.9%) subjects had CAA: 218 (68.5%) possible CAA and 33 (10.4%) probable CAA with a median number of CMB of 1.0 [1.0, 1.0]. Compared to non‐CAA subjects (n = 67), those with probable CAA at baseline were not different on demographics and vascular risk factor, had more executive dysfunction, and tended to be associated with Apoe4 status and lower hippocampal volume. After 2‐ and 4‐ years of follow‐up, 81.2% and 81.3% of the subjects still in the study had CAA, with 13.3% and 14.1% of probable CAA respectively, and the number of subjects with CMB increased to 15.9% and 18.3%.ConclusionIn the INSIGHT‐preAD study, the high frequence of CAA, with minimal change after 4 years follow‐up, was essentially due to the non‐hemorrhagic lesions. The hemorrhagic lesions (CMB and CSS) were uncommon, probably underestimated by the MRI T2* sequence. These results have implications in clinical setting and could be useful in pre‐symptomatic AD anti‐amyloid immunotherapy trial.