Cerebral amyloid angiopathy is a disease most prevalent amongst the elderly. It is associated with Alzheimer’s disease with a prevalence of 80-90%. CAA is classified into several types depending on which amyloid protein is involved but this review focuses primarily on amyloid-beta protein. CAA can mostly be found in the leptomeningeal and cortical vessels of the cerebral lobes and cerebellum. The nature of the disease is vascular in which small and medium arteries accumulate amyloid deposits into the media and adventitia of the vessel wall. Derived from the brain, amyloid moves through periarterial interstitial fluid drainage pathways to blood vessels for clearance, but aggregates on the vascular basement membrane. CAA is significantly related to lobar cerebral macrohemorrhage, as well as cerebral microbleeds, and cortical superficial siderosis. CMBs are noted in 16.7% – 32 % of AD (Alzheimer’s disease) patients, which is much higher than the general population (5 – 6%)—when examined with T2* GRE MRI; it is also noted in 78% of AD patients or mild cognitive impairment on ultra-high field strength 7T MRI. Cerebral hypoperfusion (occlusive small vessel disease may cause white matter lesions in the occipital lobe, which can be seen with MRI. Dementia is also noted in 74% of several CAA. One can image CAA with multiple modalities, for example, inflammatory CAA is characterized by T2-hyperintense white matter lesions on MRI. For macrohemorrages cranial CT is an option, however,
GRE T2* and SWI (susceptibility weighted imaging), are two of the most sensitive MR imaging techniques for detecting CMBs.
Cognitive impairment can be assessed with Doppler ultrasound and fMRI, consistent with the damage in the occipital lobe. Amyloid imaging with the PET ligand, PiB, reveals increased PiB binding which often shows greater occipital uptake of CAA-related intracerebral hemorrhage. Amyloid imaging, however, cannot discriminate between vascular from parenchymal deposition or amyloid beta from other amyloid proteins. Biochemically, levels of the amyloid tau protein are higher in patients with probable CAA compared to controls, but lower than in AD. Amyloid beta -40 and -42 levels are significantly lower in the CSF (cerebrospinal fluid) of CAA, which may suggest it is being trapped in the cerebral vasculature. The Boston criteria are used when diagnosing CAA, but no disease-modifying therapies are available yet. The risk factors for CAA include old age, AD, blood-thinners and anti-thrombotic medications, hypertension, head trauma, CAA-related gene mutations, and apolipoprotein E gene in sporadic cases. Pathogenic mechanisms underlying the damage and rupture of CAA-affected vessels remains to be determined.
Written by: Dr. E. Mark Haacke
Reference: Yamada M. Cerebral amyloid angiopathy: emerging concepts. J Stroke. 2015;17(1):17-30.
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