Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage

Abstract

Objective: Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease (SVD). Patients without intracerebral hemorrhage (ICH) typically present with transient focal neurologic episodes (TFNEs) or cognitive symptoms. We sought to determine if SVD lesion burden differed between patients with CAA first presenting with TFNEs vs cognitive symptoms.Methods: A total of 647 patients presenting either to a stroke department (n 5 205) or an outpatient memory clinic (n 5 442) were screened for eligibility. Patients meeting modified Boston criteria for probable CAA were included and markers of SVD were quantified, including cerebral microbleeds (CMBs), perivascular spaces, cortical superficial siderosis (cSS), and white matter hyperintensities (WMHs). Patients were classified according to presentation symptoms (TFNEs vs cognitive). Total CAA-SVD burden was assessed using a validated summary score. Individual neuroimaging markers and total SVD burden were compared between groups using univariable and multivariable models.Results: There were 261 patients with probable CAA included. After adjustment for confounders, patients first seen for TFNEs (n 5 97) demonstrated a higher prevalence of cSS (p , 0.0001), higher WMH volumes (p 5 0.03), and a trend toward higher CMB counts (p 5 0.09). The total SVD summary score was higher in patients seen for TFNEs (adjusted odds ratio per additional score point 1.46, 95% confidence interval 1.16-1.84, p 5 0.013). Conclusions:Patients with probable CAA without ICH first evaluated for TFNEs bear a higher burden of structural MRI SVD-related damage compared to those first seen for cognitive symptoms. This study sheds light on neuroimaging profile differences across clinical phenotypes of patients with CAA without ICH. Neurology ® 2017;88:878-884 GLOSSARY BG 5 basal ganglia; CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; CMB 5 cerebral microbleed; CSO 5 centrum semiovale; cSS 5 cortical superficial siderosis; FLAIR 5 fluid-attenuated inversion recovery; ICH 5 intracerebral hemorrhage; IQR 5 interquartile range; OR 5 odds ratio; PVS 5 perivascular spaces; SVD 5 small vessel disease; TE 5 echo time; TFNE 5 transient focal neurologic episode; WMH 5 white matter hyperintensity.Sporadic cerebral amyloid angiopathy (CAA) is characterized by progressive deposition of b-amyloid in the walls of cortical and leptomeningeal small arteries, resulting in vessel dysfunction and brain parenchymal injury. CAA is common in older individuals and, when severe, can lead to devastating consequences including intracerebral hemorrhage (ICH) and dementia. 1,2While definite diagnosis relies on pathology, clinical and neuroimaging criteria (the Boston criteria) can reliably identify CAA in older patients with lobar hemorrhage.3,4 More recently, an updated version of these criteria has demonstrated that the presence of $2 lobar cerebral microbleeds (CMBs) in patients without large hemorrhage is specific for moderate to severe CAA pathology presence in older individuals seen in a h...

Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers

“…In this context, converging body of evidence indicates that the various neuroimaging expressions of CAA may in fact be indicators for different disease phenotypes with varying risk for ICH incidence or recurrence. 8,9 Yet, no study has examined the relative importance of each of these markers versus the total burden of CAA-related SVD in assessing the risk of recurrent ICH.…”

Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer’s disease

“…An alternative possibility is that AD pathology directly promotes vascular structural or functional changes. For example, measures of cerebral perfusion in disease indicate that diminished blood flow correlates with the development of tau pathology ( 7 , 8 ), and amyloid deposition near vessels (cerebral amyloid angiopathy, CAA) is associated with MRI signatures of small vessel disease ( 9 ).…”

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

“…Clinically diagnosed CAA without ICH irst evaluated for the recurrent neurologic de icits bear a higher burden of cortical super icial siderosis, white matter changes, and a trend with increased microbleed [14]. Since CAA is often diagnosed when the characteristic MRI indings are picked up incidentally, recognizing this as a potential "TIA mimic" will be important for guiding treatment due to its higher risk of bleeding.…”