Abstract
ObjectivesThis 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).MethodsEleven 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.ResultsFunctional 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.ConclusionsThis 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.Key Points• The clinical applicability of quantitative brain imaging measures for early-stage and follow-up differential diagnosis of dementia subtypes was explored using a group-wise approach.• Quantitative tract-specific microstructural white matter abnormalities, but not quantitative functional connectivity of the default mode network, may aid early-stage and follow-up differential diagnosis of behavioural variant frontotemporal dementia and Alzheimer’s disease.• Pronounced microstructural white matter (WM) changes in anterior WM tracts characterise behavioural variant frontotemporal dementia, whereas microstructural WM abnormalities of the hippocampal cingulum in the absence of other WM changes characterise Alzheimer’s disease.
Highlights
Presenile dementia is a dementia with an onset before the age of 65 years
white matter (WM) tracts known to be associated with cognitive functions were selected for tractography: anterior thalamic radiation (ATR) [21], cingulum (CGH and CGC) [22], forceps major (FMA) [21], forceps minor (FMI) [21, 23], inferior fronto-occipital fasciculus (IFOF) [24, 25], inferior longitudinal fasciculus (ILF) [24, 25], superior longitudinal fasciculus (SLF) [26, 27] and uncinate fasciculus (UF) [22, 23, 25]
We explored group-wise quantitative measures of tract-specific WM microstructure and functional connectivity of the default mode network (DMN) to provide an initial indication of their diagnostic utility for early-stage and over time differentiation of Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD)
Summary
Presenile dementia is a dementia with an onset before the age of 65 years. The two most common underlying disorders are Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD) [1]. In later stages of AD and bvFTD, predominance of cognitive impairment in AD and social/executive impairment in bvFTD [4, 5] aids differential diagnosis. BvFTD patients may present with memory deficits [6, 7] and AD patients with changes in social behaviour or executive functioning [5, 7, 8]. Magnetic resonance imaging (MRI) supports diagnosis, but in early disease stages, conventional (structural) MRI may still appear normal or show diffuse brain abnormalities unspecific for a dementia subtype [9,10,11]. More advanced MRI techniques, such as diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI), may aid differential diagnosis by detecting more subtle abnormalities that remain unrevealed using structural MRI [12]
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