Exploring quantitative group-wise differentiation of Alzheimer's disease and behavioural variant frontotemporal dementia using tract-specific microstructural white matter and functional connectivity measures at multiple time points

Objectives This study explored group-wise quantitative measures of tract-specific white matter (WM) microstructure and functional default mode network (DMN) connectivity to establish an initial indication of their clinical applicability for early-stage and follow-up differential diagnosis of Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Methods Eleven AD and 12 bvFTD early-stage patients and 18 controls underwent diffusion tensor imaging and resting state functional magnetic resonance imaging at 3 T. All AD and 6 bvFTD patients underwent the same protocol at 1-year follow-up. Functional connectivity measures of DMN and WM tract-specific diffusivity measures were determined for all groups. Exploratory analyses were performed to compare all measures between the three groups at baseline and between patients at follow-up. Additionally, the difference between baseline and follow-up diffusivity measures in AD and bvFTD patients was compared. Results Functional connectivity of the DMN was not different between groups at baseline and at follow-up. Diffusion abnormalities were observed widely in bvFTD and regionally in the hippocampal cingulum in AD. The extent of the differences between bvFTD and AD was diminished at follow-up, yet abnormalities were still more pronounced in bvFTD. The rate of change was similar in bvFTD and AD. Conclusions This study provides a tentative indication that quantitative tract-specific microstructural WM abnormalities, but not quantitative functional connectivity of the DMN, may aid early-stage and follow-up differential diagnosis of bvFTD and AD. Specifically, pronounced microstructural changes in anterior WM tracts may characterise bvFTD, whereas microstructural abnormalities of the hippocampal cingulum may characterise AD.

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