A practical approach to the management of cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy is a common small vessel disease in the elderly involving vascular amyloid-β deposition. Cerebral amyloid angiopathy is one of the leading causes of intracerebral hemorrhage and a significant contributor to age-related cognitive decline. The awareness of a diagnosis of cerebral amyloid angiopathy is important in clinical practice as it impacts decisions to use lifelong anticoagulation or nonpharmacological alternatives to anticoagulation such as left atrial appendage closure in patients who have concurrent atrial fibrillation, another common condition in older adults. This review summarizes the latest literature regarding the management of patients with sporadic cerebral amyloid angiopathy, including diagnostic criteria, imaging biomarkers for cerebral amyloid angiopathy severity, and management strategies to decrease intracerebral hemorrhage risk. In a minority of patients, the presence of cerebral amyloid angiopathy triggers an autoimmune inflammatory reaction, referred to as cerebral amyloid angiopathy-related inflammation, which is often responsive to immunosuppressive treatment in the acute phase. Diagnosis and management of cerebral amyloid angiopathy-related inflammation will be presented separately. While there are currently no effective therapeutics available to cure or halt the progression of cerebral amyloid angiopathy, we discuss emerging avenues for potential future interventions.

Keywords: Cerebral amyloid angiopathy; cortical superficial siderosis; intracerebral hemorrhage; microbleeds; microinfarcts; small vessel disease.

Figure 1.. Hemorrhagic and non-hemorrhagic lesions associated with CAA.

Representative scans from multiple patients with probable CAA are shown. Top row (left to right): Non-contrast CT scan, susceptibility-weighted MRI, susceptibility-weighted MRI, susceptibility-weighted MRI. Bottom row (left to right): T2-weighted FLAIR MRI, T2-weighted MRI, diffusion-weighted MRI, T2-weighted FLAIR MRI. Arrows point to representative examples of each lesion in each panel.

Figure 2.. Florbetapir-PET scans from representative patients with CAA and hypertensive arteriopathy.

Left: Scan from a patient with CAA demonstrating decreased gray-white contrast, indicating increased gray matter florbetapir uptake (positive scan). Right: Scan from a patient with hypertensive arteriopathy demonstrating clear gray-white contrast throughout (negative scan). HTN = hypertension. [Adapted from Gurol et al., Neurology 2016]

Figure 3.. Managing comorbidities in patients with CAA to reduce intracerebral hemorrhage risk.

Recommendations for management of cardiovascular risk factors in patients with CAA (A); Possible alternatives to lifelong anticoagulation in patients with CAA, based on the clinical indication (B). Individualized decisions regarding anticoagulation should be made through multidisciplinary discussions, involving patients and families. Key: BP = blood pressure; ACC/AHA = American College of Cardiology/American Heart Association; DVT = deep vein thrombosis; PE = pulmonary embolism; IVC = inferior vena cava; LAAC = left atrial appendage closure; APLAS = antiphospholipid antibody syndrome.

Figure 4.. CAA pathogenesis and potential targets for intervention.

Amyloid-β (Aβ) deposits and precursors shown in blue; potential interventions at each stage shown in orange. A tangential cross-section of a diving arteriole is depicted; pial surface to the right of the figure.