White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

Resting-state functional MRI of the visual system for characterization of optic neuropathy.

Optic neuropathy refers to disease of the optic nerve and can result in loss of visual acuity and/or visual field defects. Combining findings from multiple fMRI modalities can offer valuable information for characterizing and managing optic neuropathies. In this article, we review a subset of resting-state functional magnetic resonance imaging (RS-fMRI) studies of optic neuropathies. We consider glaucoma, acute optic neuritis (ON), discuss traumatic optic neuropathy (TON), and explore consistency between findings from RS and visually driven fMRI studies. Consistent with visually driven studies, glaucoma studies at rest also indicated reduced activation in the visual cortex and dorsal visual stream. RS-fMRI further reported varying levels of functional connectivity in the ventral stream depending on disease severity. ON patients show alterations within the visual cortex in both fMRI techniques. Particularly, higher-than-normal RS activity is observed in the acute phase and decreases as the disease progresses. A similar pattern is observed in the visual cortex of TON-like, open globe injury (OGI), patients. Additionally, visually driven and RS-fMRI studies of ON patients show recovery of brain activity in the visual cortex. RS-fMRI suggests recovery of signals in higher-tier visual areas MT and LOC as well. Finally, RS-fMRI has not yet been applied to TON, although reviewing OGI studies suggests that it is feasible. Future RS-fMRI studies of optic neuropathies could prioritize studying the fine scale RS activity of brain areas that visually driven studies have identified. We suggest that a more systematic longitudinal comparison of optic neuropathies with advanced fMRI would provide improved diagnostic and prognostic information.

Visually driven functional MRI techniques for characterization of optic neuropathy.

Optic neuropathies are conditions that cause disease to the optic nerve, and can result in loss of visual acuity and/or visual field defects. An improved understanding of how these conditions affect the entire visual system is warranted, to better predict and/or restore the visual loss. In this article, we review visually-driven functional magnetic resonance imaging (fMRI) studies of optic neuropathies, including glaucoma and optic neuritis (ON); we also discuss traumatic optic neuropathy (TON). Optic neuropathy-related vision loss results in fMRI deficit within the visual cortex, and is often strongly correlated with clinical severity measures. Using predominantly flickering checkerboard stimuli, glaucoma studies indicated retinotopic-specific cortical alteration with more prominent deficits in advanced than in early glaucoma. Some glaucoma studies indicate a reorganized visual cortex. ON studies have indicated that the impacted cortical areas are briefly hyperactive. For ON, brain deficits are greater in the acute stages of the disease, followed by (near) normalization of responses of the LGN, visual cortex, and the dorsal visual stream, but not the ventral extrastriate cortex. Visually-driven fMRI is sensitive, at least in ON, in discriminating patients from controls, as well as the affected eye from the fellow eye within patients. The use of a greater variety of stimuli beyond checkerboards (e.g., visual motion and object recognition) in recent ON studies is encouraging, and needs to continue to disentangle the results in terms of change over time. Finally, visually-driven fMRI has not yet been applied in TON, although preliminary efforts suggest it may be feasible. Future fMRI studies of optic neuropathies should consider using more complex visual stimuli, and inter-regional analysis methods including functional connectivity. We suggest that a more systematic longitudinal comparison of optic neuropathies with advanced fMRI would provide improved diagnostic and prognostic information.

Increased brain volumetric measurement precision from multi-site 3D T1-weighted 3 T magnetic resonance imaging by correcting geometric distortions.

PURPOSE: Magnetic resonance imaging (MRI) scanner-specific geometric distortions may contribute to scanner induced variability and decrease volumetric measurement precision for multi-site studies. The purpose of this study was to determine whether geometric distortion correction increases the precision of brain volumetric measurements in a multi-site multi-scanner study. METHODS: Geometric distortion variation was quantified over a one-year period at 10 sites using the distortion fields estimated from monthly 3D T1-weighted MRI geometrical phantom scans. The variability of volume and distance measurements were quantified using synthetic volumes and a standard quantitative MRI (qMRI) phantom. The effects of geometric distortion corrections on MRI derived volumetric measurements of the human brain were assessed in two subjects scanned on each of the 10 MRI scanners and in 150 subjects with cerebrovascaular disease (CVD) acquired across imaging sites. RESULTS: Geometric distortions were found to vary substantially between different MRI scanners but were relatively stable on each scanner over a one-year interval. Geometric distortions varied spatially, increasing in severity with distance from the magnet isocenter. In measurements made with the qMRI phantom, the geometric distortion correction decreased the standard deviation of volumetric assessments by 35% and distance measurements by 42%. The average coefficient of variance decreased by 16% in gray matter and white matter volume estimates in the two subjects scanned on the 10 MRI scanners. CONCLUSION: Geometric distortion correction using an up-to-date correction field is recommended to increase precision in volumetric measurements made from MRI images.

Comparison of Diffusion Tensor Imaging Metrics in Normal-Appearing White Matter to Cerebrovascular Lesions and Correlation with Cerebrovascular Disease Risk Factors and Severity.

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.