Characterizing mixed location hemorrhages/microbleeds with CSF markers.

ObjectiveCerebral Amyloid Angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A).They are an exclusion criterion for CAA, and whne present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLH). We compared clinical, radiological and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer's Disease (AD) and healthy controls (HC) and used it to position MLH in the disease spectrum.Patients and MethodsRetrospective cohort study of consecutive patients with CAA (n=31), MLH (n=31), AD (n=28) and HC (n=30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau and p-tau), and histopathological data in patients each group.ResultscSS was significantly more common in CAA than MLH (45% vs. 13%, p = 0.011), and cSS in MLH was associated with ICH (p = 0.037). Aß42 levels and and the Aß42/Aß40 ratio, diagnostic groups followed the order HC > MLH > CAA > AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without.ConclusionOur data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.