Background: Patients with Cerebral Amyloid Angiopathy (CAA) have posterior vascular amyloid deposition and lower Amyloid Beta (Aβ) levels when compared to Alzheimer’s Disease (AD). We hypothesized that similar findings would be observed in AD patients with strictly lobar microbleeds (LMB) and/or cortical superficial siderosis (cSS) attributable to CAA [CAA-AD], when compared to AD with no hemorrhagic lesion [NH-AD].
Methods: We reviewed brain MRIs of patients with AD who had T2*-, FLAIR and 3D T1-weighted MRI as well as Florbetapir PET, CSF Aβ-42 and tau levels, and APOE status within the ADNI database. We compared the demographics, quantitative imaging and lab findings of CAA-AD to NH-AD.
Results: The CAA-AD (n=51) and NH-AD (n=85) groups were balanced for age, gender and history of hypertension (all p>0.2). The APOE4 was more frequently present in the CAA-AD group (78% vs 60%, p=0.038), no difference for APOE2 (p=0.41). Patients with CAA-AD had higher WMH volume (0.73 vs 0.49 % intracranial volume [ICV], p=0.035) and higher occipital-to-global Florbetapir ratio (0.98 vs 0.94, p=0.02) but similar mean cortical Florbetapir uptake (1.38 vs 1.36, p=0.57), cortical thickness (2.22 vs 2.20 mm, p=0.38), and hippocampal volume (0.37 vs 0.38 % of ICV, p=0.24) when compared to NH-AD. In a multivariable regression model that included all variables above, higher occipital-to-global Florbetapir ratio (p=0.009) and presence of APOE4 (p=0.002) were associated with CAA-AD, higher WMH (p=0.097) showed a trend. In 117 patients with CSF data, CAA-AD (n=46) had lower Aβ-42 (127 vs 140 pg/ml, p=0.038) but similar tau levels (131 vs 136 pg/ml, p=0.68) when compared to NH-AD. Lower Aβ-42 was associated with CAA-AD (p=0.024) in the relevant multivariate regression model.
Conclusions: Over one-third of patients with AD displayed subtle hemorrhagic lesions in a CAA-pattern on MRI. When compared to NH-AD, they have higher occipital Florbetapir uptake suggesting vascular amyloid binding and lower CSF Aβ-42 levels that might be related to sequestering of amyloid in cortical vessel walls. These results support the possibility that advanced CAA commonly accompanies clinically diagnosed AD, contributing to dementia pathogenesis and potentially affecting clinical treatment decisions.