A graph theoretic approach to neurodegeneration: five data-driven neuropsychological subtypes in mild cognitive impairment.

Mild cognitive Impairment (MCI) is notoriously heterogenous in terms of clinical presentation, neuroimaging correlates, and subsequent progression. Predicting who will progress to dementia, which type of dementia, and over what timeframe is challenging. Previous work has attempted to identify MCI subtypes using neuropsychological measures in an effort to address this challenge; however, there is no consensus on approach, which may account for some of the variability. Using a hierarchical community detection approach, we examined cognitive subtypes within an MCI sample (from the Alzheimer's Disease Neuroimaging Initiative [ADNI] study). We then examined whether these subtypes were related to biomarkers (e.g., cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. We identified five communities (i.e., cognitive subtypes) within the MCI sample: 1) predominantly memory impairment, 2) predominantly language impairment, 3) cognitively normal, 4) multidomain, with notable executive dysfunction, 5) multidomain, with notable processing speed impairment. Community membership was significantly associated with 1) cortical volume in the hippocampus, entorhinal cortex, and fusiform cortex; 2) FDG PET hypometabolism in the posterior cingulate, angular gyrus, and inferior/middle temporal gyrus; and 3) conversion to dementia at follow up. Overall, community detection as an approach appears a viable method for identifying unique cognitive subtypes in a neurodegenerative sample that were linked to several meaningful biomarkers and modestly with progression at one year follow up.

Relationship between cognitive reserve, brain volume, and neuropsychological performance in amnestic and nonamnestic MCI.

Cognitive Reserve (CR) is a theoretical construct that influences the onset and course of cognitive and structural changes that occur with aging and mild cognitive impairment (MCI). There is a paucity of research that examines the relationship of CR and brain volumes in amnestic (aMCI) and nonamnestic (naMCI) separately. This study is a retrospective chart review of MCI patients who underwent neuropsychological evaluation and brain MRI with NeuroReader™ (NR). NR is an FDA-cleared software that standardizes MRI volumes to a control sample. Classifications of aMCI and naMCI were based on Petersen criteria. CR was measured as education, occupation, and word reading. Data analysis included bivariate correlations between CR, neuropsychological test scores, and NR-brain volumes by MCI subtype. The Benjamini-Hochberg method corrected for multiple comparisons. The sample included 91 participants with aMCI and 41 with naMCI. Within naMCI, positive correlations were observed between CR and whole brain volume, total gray matter, bifrontal, left parietal, left occipital, and bilateral cerebellum. Within aMCI, no significant correlations were observed between CR and brain volumes. Positive correlations with CR were observed in language, attention, and visual learning in both aMCI and naMCI groups. The current study adds to the minimal literature on CR and naMCI. Results revealed that CR is associated with volumetrics in naMCI only, though cognitive findings were similar in both MCI groups. Possible explanations include heterogeneous disease pathologies, disease stage, or a differential influence of CR on volumetrics in MCI. Additional longitudinal and biomarker studies will better elucidate this relationship.

Filtered Diffusion-Weighted MRI of the Human Cervical Spinal Cord: Feasibility and Application to Traumatic Spinal Cord Injury.

BACKGROUND AND PURPOSE: In traumatic spinal cord injury, DTI is sensitive to injury but is unable to differentiate multiple pathologies. Axonal damage is a central feature of the underlying cord injury, but prominent edema confounds its detection. The purpose of this study was to examine a filtered DWI technique in patients with acute spinal cord injury. MATERIALS AND METHODS: The MR imaging protocol was first evaluated in a cohort of healthy subjects at 3T (n = 3). Subsequently, patients with acute cervical spinal cord injury (n = 8) underwent filtered DWI concurrent with their acute clinical MR imaging examination <24 hours postinjury at 1.5T. DTI was obtained with 25 directions at a b-value of 800 s/mm2. Filtered DWI used spinal cord-optimized diffusion-weighting along 26 directions with a "filter" b-value of 2000 s/mm2 and a "probe" maximum b-value of 1000 s/mm2. Parallel diffusivity metrics obtained from DTI and filtered DWI were compared. RESULTS: The high-strength diffusion-weighting perpendicular to the cord suppressed signals from tissues outside of the spinal cord, including muscle and CSF. The parallel ADC acquired from filtered DWI at the level of injury relative to the most cranial region showed a greater decrease (38.71%) compared with the decrease in axial diffusivity acquired by DTI (17.68%). CONCLUSIONS: The results demonstrated that filtered DWI is feasible in the acute setting of spinal cord injury and reveals spinal cord diffusion characteristics not evident with conventional DTI.

Quantitative Susceptibility Mapping after Sports-Related Concussion.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping using MR imaging can assess changes in brain tissue structure and composition. This report presents preliminary results demonstrating changes in tissue magnetic susceptibility after sports-related concussion. MATERIALS AND METHODS: Longitudinal quantitative susceptibility mapping metrics were produced from imaging data acquired from cohorts of concussed and control football athletes. One hundred thirty-six quantitative susceptibility mapping datasets were analyzed across 3 separate visits (24 hours after injury, 8 days postinjury, and 6 months postinjury). Longitudinal quantitative susceptibility mapping group analyses were performed on stability-thresholded brain tissue compartments and selected subregions. Clinical concussion metrics were also measured longitudinally in both cohorts and compared with the measured quantitative susceptibility mapping. RESULTS: Statistically significant increases in white matter susceptibility were identified in the concussed athlete group during the acute (24 hour) and subacute (day 8) period. These effects were most prominent at the 8-day visit but recovered and showed no significant difference from controls at the 6-month visit. The subcortical gray matter showed no statistically significant group differences. Observed susceptibility changes after concussion appeared to outlast self-reported clinical recovery metrics at a group level. At an individual subject level, susceptibility increases within the white matter showed statistically significant correlations with return-to-play durations. CONCLUSIONS: The results of this preliminary investigation suggest that sports-related concussion can induce physiologic changes to brain tissue that can be detected using MR imaging-based magnetic susceptibility estimates. In group analyses, the observed tissue changes appear to persist beyond those detected on clinical outcome assessments and were associated with return-to-play duration after sports-related concussion.