Cerebral amyloid angiopathy diagnosis

Pathologic deposition of beta amyloid protein (appears as birefringent “apple-green” under polarized light when stained with congo red) within the media of small meningeal and cortical vessels (especially those in white matter) without evidence of systemic amyloidosis.

Intracerebral macrohemorrhages (ICH) are the most important clinical presentation, and cerebral microbleeds (MBs) are a common magnetic resonance sign of CAA.

Much attention has been paid that cerebral amyloid angiopathy in cortical and leptomeningeal arteries blocks the flow of interstitial fluid along the wall of arteries in the white matter with consequent derangement of the perivascular space, deposition of beta-amyloid, and Alzheimer's disease pathology ¹⁾.

These processes may explain why perivascular space becomes narrow (this process occurs predominantly at the centrum semiovale), why periventricular white matter hyperintensity in MRI is shunt-responsive and considerably reversible in iNPH brains ²⁾.

CAA should be suspected in patients with recurrent hemorrhages (uncommon with “hypertensive hemorrhages” that are lobar in location.

May be useful later, e.g. to help diagnose cerebral amyloid angiopathy (CAA).

Gradient-echo MRI may identify petechial hemorrhages (microbleeds) or hemosiderin deposits from small cortical hemorrhages. Less likely in the case of basal ganglion or brain stem hemorrhages.

Among patients with lobar hemorrhage, those with the apoE ε4 allele typically have their first hemorrhage > 5 yrs earlier than noncarriers (73 ± 8 yrs vs./ 79 ± 7 yrs).

Cerebral amyloid angiopathy have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer's disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer's and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings ³⁾.