Peak width of skeletonized mean diffusivity as a biomarker of small vessel disease in predementia Alzheimer's disease

Introduction: Alzheimer's disease (AD) and cerebral small vessel disease (SVD) frequently coexist, and increasing evidence suggest that microvascular changes may be related to AD pathology. SVD is however heterogeneously expressed on magnetic resonance imaging (MRI), and several novel methods can determine different aspects of vascular pathology. These methods need to be explored properly in clinical AD cohorts to better understand the link between AD and SVD, and could possibly be included in the staging and diagnostics of AD. Methods: 588 subjects were included from the Norwegian Dementia Disease initiation (DDI) cohort, longitudinal data was available for 285 subjects. Subjects underwent clinical examination including lumbar puncture, and were classified according to the A/T/N-system into the following groups: A-/T-/N- (N=208), A-/T+/N± (N=11), A+/T-/N- (N=75)and A+/T+/N±(N=157) according to positive (+) or negative (-) values of cerebrospinal fluid (CSF) amyloid-β42/40-ratio (A), phosphorylated-tau (T) and total-tau (N)). We used Peak width of skeletonized mean diffusivity (PSMD), a novel MRI Diffusion Tensor Imaging (DTI) method for determination of global SVD-burden based on an automated algorithm (5). We used a mixed linear regression model to determine baseline and longitudinal differences in PSMD across A/T/N-classified subjects in a predementia cohort, adjusted for subject and scanner as a random effect. Results: Compared to A-/T-/N- at baseline, we found significantly larger SVD burden in A+/T-/N- compared to A-/T-/N- (p