To quantify the level of brain ¹⁸F-florbetapir uptake in patients with cerebral amyloid angiopathy (CAA), and investigate its relationship with neuroimaging markers of cerebral small vessel disease.

This study enrolled patients from a prospective cerebral small vessel disease cohort study at Peking Union Medical College Hospital between January 2021 and March 2024. The patients met the diagnosis criteria for ''probable CAA'' according to the Boston criteria version 1.5. Additionally, two patients diagnosed with CAA-related inflammation (CAA-ri) were also included. All participants underwent 3.0T MRI and ¹⁸F-florbetapir PET/CT within 1 month of their diagnosis. PET images were analyzed both visually and quantitatively. The standardized uptake value ratio (SUVr) of regions of interest was calculated using white matter as the reference region. Demographic characteristics, clinical, laboratory, MRI, and PET imaging data were collected from all patients. The relationship between ¹⁸F-florbetapir uptake and MRI markers was analyzed, including hemorrhagic markers such as strict lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), convexal subarachnoid hemorrhage (cSAH), and non-hemorrhagic markers white matter hyperintensity (WMH). Patients with CAA were classified into three groups according to clinical and neuroimaging characteristics: CAA-related intracranial hemorrhage (ICH), CAA with cognitive impairment, and CAA-ri. We used one-way ANOVA to compare the differences in global cerebral cortex SUVr and cerebellar cortex SUVr among the three groups. Student's t-test was used to compare the global cerebral or cerebellar cortex SUVr between patients grouped by the count of strict lobar CMBs, WMH Fazekas, and cerebellar CMBs. The Mann-Whitney U test was used to compare global cortical SUVr between patients with and without cSS/cSAH.

Thirty-six patients with CAA were included in this study, with a mean age of (67.94±8.10) years, and 69.4% were male. Patients were classified into three subtypes: CAA-related ICH (n=9, 25.0%), CAA with cognitive impairment (n=21, 58.3%), and CAA-ri (n=6, 16.7%). The ¹⁸F-florbetapir SUVr for CAA with cognitive impairment and CAA-related ICH were 0.89±0.13 and 0.84±0.16, respectively (P>0.05). The ¹⁸F-florbetapir SUVr of CAA with cSS/cSAH was significantly lower than those without cSS/cSAH [0.78(0.74, 0.86) vs 0.90(0.84, 0.99), U=-2.322, P=0.02]. The ¹⁸F-florbetapir SUVr in CAA with amount of strict lobar CMBs ≥5 and 0~4 were 0.88±0.13 and 0.83±0.12, respectively (P>0.05), and that in CAA with severe WMH and mild WMH were 0.90±0.14 and 0.83±0.11, respectively (P>0.05). The cerebellar cortex SUVr in patients with and without cerebellar CMBs were 0.79±0.11 and 0.74±0.14, respectively (P>0.05).

Patients with CAA exhibiting lobar ICH or cSS/cSAH demonstrated lower global cerebral ¹⁸F-florbetapir uptake, whereas those with a higher number of strict lobar CMBs and severe WMH might exhibit greater ¹⁸F-florbetapir uptake. This suggests that the condition of ¹⁸F-florbetapir uptake could be potentially associated with distinct clinical and imaging phenotypes with different pathogenic mechanisms.