We aimed to determine whether free water (FW) is elevated in cerebral amyloid angiopathy (CAA) compared to non-CAA participants and to assess FW's neuroimaging and cognitive associations in CAA compared to other conventional magnetic resonance imaging (MRI) markers of cerebral small vessel disease (cSVD).

Participants were recruited from a memory-clinic cohort, and were stratified into CAA and non-CAA groups. FW was computed using a freely available pipeline. Diffusion metrics were analyzed within the white matter skeleton, using tract-based spatial statics. We compared FW values between the groups. Within the CAA group, we explored FW's association with conventional MRI markers of cSVD and with cognitive scores in multiple domains.

Eighty-eight CAA [mean age 75.6(54.9-95.9) years; 47.7% female] and 38 non-CAA subjects [mean age 71.6(56.3-86.1) years; 44.7% female] were included in the analysis. FW values were higher (0.24±0.04; mean ± SD) in the CAA than in the non-CAA group (0.18±0.03; p <0.0001). Within the CAA group, in multivariable regression analyses adjusted for age, FW was associated with cerebral microbleeds (β=0.0003, p=0.006), white matter hyperintensities volume (β=12.57, p=<0.0001), cortical superficial siderosis (β=0.08, p=0.03), perivascular spaces in the centrum semiovale  (β=0.14, p=0.0002) and brain volume (β=-0.88, p=0.05). In simple linear regression model, FW was associated with executive function (EF) (β=-8.23, p=0.02) and Mini-Mental State Examination (MMSE) (β=-18.2, p=0.05).

Participants with CAA have higher FW values compared to non-CAA. In CAA participants, FW is significantly associated with conventional MRI markers of cSVD, with EF and with MMSE.