Sensitivity of restriction spectrum imaging to memory and neuropathology in Alzheimer’s disease

Abstract

BackgroundDiffusion imaging has demonstrated sensitivity to structural brain changes in Alzheimer’s disease (AD). However, there remains a need for a more complete characterization of microstructural alterations occurring at the earliest disease stages, and how these changes relate to underlying neuropathology. This study evaluated the sensitivity of restriction spectrum imaging (RSI), an advanced diffusion magnetic resonance imaging (MRI) technique, to microstructural brain changes in mild cognitive impairment (MCI) and AD.MethodsMRI and neuropsychological test data were acquired from 31 healthy controls, 12 individuals with MCI, and 13 individuals with mild AD, aged 63–93 years. Cerebrospinal fluid amyloid-β levels were measured in a subset (n = 38) of participants. RSI measures of neurite density (ND) and isotropic free water (IF) were computed in fiber tracts and in hippocampal and entorhinal cortex gray matter, respectively. Analyses evaluated whether these measures predicted memory performance, correlated with amyloid-β levels, and distinguished impaired individuals from controls. For comparison, analyses were repeated with standard diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA) and mean diffusivity.ResultsBoth RSI and DTI measures correlated with episodic memory and disease severity. RSI, but not DTI, measures correlated with amyloid-β42 levels. ND and FA in the arcuate fasciculus and entorhinal cortex IF most strongly predicted recall performance. RSI measures of arcuate fasciculus ND and entorhinal cortex IF best discriminated memory impaired participants from healthy participants.ConclusionsRSI is highly sensitive to microstructural changes in the early stages of AD, and is associated with biochemical markers of AD pathology. Reduced ND in cortical association fibers and increased medial temporal lobe free-water diffusion predicted episodic memory, distinguished cognitively impaired from healthy individuals, and correlated with amyloid-β. Although further research is needed to assess the sensitivity of RSI to preclinical AD and disease progression, these results suggest that RSI may be a promising tool to better understand neuroanatomical changes in AD and their association with neuropathology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0281-7) contains supplementary material, which is available to authorized users.

Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease

“… Gomar, et al 2017 [40] 9 aMCI, 9 ADD, 44 CNC Relational and item-specific encoding task Entorhinal, perirhinal, parahippocampal cortices thickness, HC volumetry HC volume, perirhinal and parahippocampal thickness predicted encoding performance. Reas, et al 2017 [41] 12 MCI, 13 ADD, 31 CNC WMS-R, CVLT, CERAD Restriction spectrum imaging in fiber tracts, HC and entorhinal cortex GM; DTI Fornix, uncinated, inferior fronto-occipital, inferior longitudinal and arcuate fasciculi neurite density positively correlated with recall. HC and entorhinal cortex isotropic free water diffusion negatively correlated with memory.…”

“…Similar to GM changes, which include both MTL and extratemporal regions, precuneus WM volume reduction was also associated with worsened memory in aMCI [18] . Several fasciculi including uncinate, fornix, and cingulum, which are connected to medial temporal regions, were implicated in studies associating fiber density and memory [20] , [22] , [41] . In addition to these WM volume and integrity changes, Fujishima et al [19] reported that increased number of WMHs, pointing to increased vascular impairment, in the bilateral periventricular regions was related to worse recall performance in MCI.…”

White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction

“…Thirdly, we looked at the derivatives of each function of the lme models' age curve to identify the point of change in trajectory for each diffusion metric. Based on previous work characterising age differences and longitudinal changes with a range of diffusion MRI metrics (Benitez et al, 2018;Falangola et al, 2008;Jelescu et al, 2015;Kodiweera et al, 2016;Reas et al, 2017;Westlye et al, 2010), we expected the included metrics to show curvilinear relationships with age, with varying trajectories and deflection points possibly reflecting differential involvement and rate of change of the putative biological underpinnings during the different phases of brain ageing.…”

Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis

“…19 RSI and NODDI have similar approach (multishell acquisition and multicompartment diffusion model); however, whereas NODDI characterizes the degree of fiber dispersion, RSI further identifies the geometric pattern of dispersion and has a more efficient acquisition time. 17,30 The association we observe between RSIderived parameters and disability is very interesting, since an MRI-biomarker for disability in MS is much needed. Clinical disability assessment using EDSS has been criticized, because EDSS mainly reflects motoric disability.…”