The Longitudinal Decline of White Matter Microstructural Integrity in Behavioral Variant Frontotemporal Dementia and Its Association with Executive Function

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Background: Previous longitudinal research has observed a decline in the integrity of several white matter (WM) tracts in behavioral variant frontotemporal dementia (bvFTD). However, without a clear relationship between these WM changes and observable behavioral changes, such as the decline in executive function (EF), it is unclear how these WM changes meaningfully reflect progression in bvFTD. The current study sought to validate the use of diffusion tensor imaging (DTI) in tracking the progression of bvFTD with its associated decline in EF. Methods: DTI scans were acquired at baseline and one-year follow-up from 23 patients with bvFTD and 26 healthy controls from the FTLDNI dataset. EF composite scores were derived multiple EF tests via confirmatory factor analysis on the larger FTLDNI dataset. The longitudinal changes in fractional anisotropy (FA) and mean diffusivity (MD) were examined via tract-based spatial statistics, separately, in both groups. FA and MD changes across time in bvFTD were regressed on EF changes. Results: Widespread clusters of significant FA decrease and MD increase, and a significant decline in EF scores were observed in patients with bvFTD, but not healthy controls. This EF decline was mostly associated with FA decrease and MD increase in the corpus callosum and anterior corona radiata. Conclusions: The bvFTD-associated decline of WM integrity was observed in several tracts, of which some were specific to EF decline. The current study presented valuable longitudinal evidence to support the use of DTI in tracking the progression of bvFTD and its associated EF decline. Funding Statement: This work is supported by funding from The University of Hong Kong May Endowed Professorship and the KKHo International Charitable Foundation. Data collection and sharing for this project was funded by the Frontotemporal Lobar Degeneration Neuroimaging Initiative (National Institutes of Health Grant R01 AG032306). The funders had no involvement in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: The authors report no conflicts of interest. Ethics Approval Statement: Ethics approval for the FTLDNI protocol have been granted by institutional review boards at their respective study sites. (Participants with FTDs underwent comprehensive neurological, neuropsychological and functional assessment, including informant interview at one of three study sites — University of California, San Francisco, Mayo Clinic, Rochester and Massachusetts General Hospital.) The FTLDNI is coordinated through the University of California, San Francisco, Memory and Aging Center. FTLDNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.