Introduction:
Peak width of skeletonized mean diffusivity (PSMD) is a novel fully automated diffusion tensor imaging (DTI) marker that has been consistently associated with cognition in cerebral small vessel disease (SVD) cohorts, including cerebral amyloid angiopathy (CAA). We hypothesized that PSMD would be more strongly associated with cognitive performance compared to other conventional DTI metrics in our CAA sample.
Methods:
We recruited non-demented subjects with probable-CAA from a single-center memory-clinic cohort. We analyzed structural MRIs to compute a validated CAA burden score (0-6 points scale, based on the following MRI features: lobar microbleeds, superficial siderosis, perivascular spaces in centrum semiovale, and white matter hyperintensities). PSMD was obtained using a freely available script (
www.psmd-marker.com
). We used the same skeleton-mask to compute: mean of skeletonized mean diffusivity (mean MD) and mean of skeletonized fractional anisotropy (mean FA). We used linear regression analyses to explore relationships with CAA burden score and cognitive composite scores (processing speed, executive function, memory, and language - z-scores adjusted for age, sex and education level).
Results:
We included 43 subjects (mean age 74.4 ± 5.9 years; 48.8% female; PSMD median [IQR]: 4.05 [3.58 - 4.80] x 10
-4
mm
2
/s). In linear regression models adjusting for age, DTI metrics were significantly associated with CAA burden score (mean FA:
β
= -0.563, Adj. R
2
: 0.27;
p
< 0.001; mean MD:
β
= 0.581; Adj. R
2
: 0.32;
p
< 0.001; PSMD:
β
= 0.364, Adj. R
2
: 0.12;
p
= 0.018). PSMD was significantly associated with cognitive performance, specifically in the domains of executive function (
β
= -0.568; Adj. R
2
: 0.25;
p
< 0.001) and processing speed (
β
= -0.447; Adj. R
2
: 0.19;
p
= 0.004). Other DTI metrics were not significantly associated with cognitive scores.
Conclusion:
In this CAA sample, all DTI metrics were associated with CAA burden scores, however, only PSMD was significantly associated with cognition, in domains that are commonly affected in vascular cognitive impairment. Our results warrant confirmation in larger samples, but support PSMD as biomarker for cognition in CAA, outperforming other conventional DTI metrics.
Neuropsychiatric correlates of cerebral amyloid burden in a memory clinic sample
