Diffusion Tensor Imaging Surpasses Cerebrospinal Fluid as Predictor of Cognitive Decline and Medial Temporal Lobe Atrophy in Subjective Cognitive Impairment and Mild Cognitive Impairment

Abstract

Neuropathological correlates of Alzheimer's disease (AD) emerge years before dementia. Biomarkers preceding cognitive decline and reflecting the causative processes can potentially aid early intervention and diagnosis. Diffusion tensor imaging (DTI) indirectly reflects tissue microstructure. To answer whether DTI is an early biomarker for AD and to explore the relationship between DTI and the established biomarkers of medial temporal lobe atrophy and cerebrospinal fluid (CSF) Aβ(42), T-tau, and P-tau, we longitudinally studied normal controls and patients with subjective (SCI) or mild (MCI) cognitive impairment. 21 controls and 64 SCI or MCI cases recruited from a university-hospital based memory clinic were re-examined after two to three years. FreeSurfer was used for longitudinal processing of morphometric data, and DTI derived fractional anisotropy, radial diffusivity, and mean diffusivity were analyzed in Tract-Based Spatial Statistics. Using regression models, we explored and compared the predictive powers of DTI and CSF biomarkers in regard to cognitive change and atrophy of the medial temporal lobe. Both DTI and CSF biomarkers significantly predicted cognitive decline and atrophy in the medial temporal lobe. In this population, however, DTI was a better predictor of dementia and AD-specific medial temporal lobe atrophy than the CSF biomarkers. The case for DTI as an early biomarker for AD is strengthened, but further studies are needed to confirm these results.

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

“…Regional diffusion measures of white matter integrity, most notably of the fornix, posterior cingulum, and parahippocampal white matter, have also shown promising accuracies between 77% and 95% for the prediction of conversion from MCI to AD dementia over clinical follow-up times of 2 to 3 years Mielke et al, 2012;Scola et al, 2010;Selnes et al, 2013). Preliminary findings further suggest that MD may be of higher predictive value compared to FA , and that diffusion metrics may be generally better predictors of conversion than volumetric measurements on structural MRI (Fellgiebel et al, 2006;Scola et al, 2010), particularly for the prediction of future cognitive impairments in cognitively normal elderly (Fletcher et al, 2013;Zhuang et al, 2012).…”

Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline

“…25 Our population-based study revealed that reduced microstructural white matter integrity was also predictive of subsequent cognitive decline, independent of WMH load. Although previous research has suggested that reduced microstructural white matter integrity in aging is largely explained by WMH, 26 our data indicated that the association between reduced white matter integrity and cognitive decline could not be accounted for by global WMH load.…”

White matter hyperintensity microstructure in amyloid dysmetabolism

“…We have previously shown that DTI is a better predictor of cognitive decline than CSF biomarkers in subjects with SCD and MCI. 13 Four common DTI indices are derived, likely reflecting different microstructural properties, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR), and axial diffusivity (DA). Although the neurobiological interpretation of the DTI indices is complex, increased DR is thought to reflect changes to axonal diameter, axonal density and myelination, while DA has been associated with the axonal integrity.…”