Differential Longitudinal Decline of White Matter Integrity in Frontotemporal Lobar Degeneration and Alzheimer’s Disease (P4.023)

Objective: To identify imaging biomarkers of disease progression in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) that can be used in longitudinal assessments. Background: Recent years have witnessed the emergence of treatment trials for FTLD and AD, creating a need for sensitive biomarkers of disease progression. Cross-sectional studies have shown that white matter integrity, measured via diffusion tensor imaging (DTI), is affected by both AD and FTLD. Few studies have quantified or compared the rates of change in white matter integrity in these disorders. Methods: Diffusion weighted 3T MRIs from a cohort of 60 FTLD patients (27 behavioral-variant, 19 semantic-variant, 14 progressive non-fluent aphasia), 19 AD, and 69 healthy age-matched controls were acquired at baseline and 1-year on average follow up. Images were processed using a longitudinal DTI pipeline implemented in SPM12 to identify annualized changes in fractional anisotropy (FA). Results: Compared to controls, FTLD showed more reduction in FA over 1-year in the corpus callosum (CC), superior longitudinal fasciculus, inferior longitudinal fasciculus, the uncinate, and anterior portions of the internal capsule and corona radiata. In AD, FA reductions were seen in the splenium and posterior portions of the thalamic radiation. Rates of decline were -0.028 FA units per year in FTLD in the genu of the CC, and -0.017 FA units per year in AD in splenium of the CC. Conclusions: Decline in white matter integrity in FTLD and AD is measurable over 1 year and reflects established patterns of brain pathology in these two disorders. This suggests that changes in white matter integrity can provide a viable surrogate marker in both FTLD and AD for future clinical trials. In addition, similar to previous clinical and volumetric studies, white matter is shown to degrade nearly twice as rapidly in FLTD compared to AD. Disclosure: Dr. Marx has nothing to disclose. Dr. Elahi has nothing to disclose. Dr. Elofson has nothing to disclose. Dr. Cobigo has nothing to disclose. Dr. Tosun has nothing to disclose. Dr. Schuff has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Rosen has nothing to disclose.