Background

Advanced cervical spondylosis (CS) can cause structural damage to the spinal cord resulting in long-term neurological impairment including neck pain and motor weakness. We hypothesized long-term structural reorganization within the brain in patients with CS.

Objective

To explore the associations between cortical thickness, subcortical volumes, neurological symptoms, and pain severity in CS patients with or without myelopathy and healthy controls (HCs).

Methods

High-resolution T1-weighted structural magnetic resonance imaging (MRI) scans from 26 CS patients and 45 HCs were acquired. Cortical thickness and subcortical volumes were computed and compared to the modified Japanese Orthopedic Association (mJOA) and the Neck Disability Index (NDI) scores.

Results

Cortical thinning within the superior frontal gyrus, anterior cingulate, precuneus, and reduction in putamen volume were associated with worsening neurological and pain symptoms. Among the strongest associations were cortical thickness within the left precuneus (R2 = 0.34) and left and right putamen (R2 = 0.43, 0.47, respectively) vs mJOA, and the left precuneus (R2 = 0.55), insula (R2 = 0.57), and right putamen (R2 = 0.54) vs NDI (P ≤ .0001 for all). Cortical thickness along Brodmann areas 3a, 4a, and 4p were also moderately associated with mJOA. Preliminary evidence also suggests that patients with CS may undergo cortical atrophy at a faster rate than HCs.

Conclusion

Patients with CS appear to exhibit cortical thinning and atrophy with worsening neurological and pain symptoms in specific brain regions associated with sensorimotor and pain processing.

Background: Alzheimer’s disease pathology (AD) is an important cause of neurodegeneration and brain atrophy. Non-AD mechanisms can also cause neurodegeneration alone or in conjunction with AD. Harboring combination of AD and non-AD pathologies leads to greater cognitive impairment and dementia. Here, we examined the hypothesis that the association of amyloid and tau burden from positron emission tomography (PET) with brain volumes from magnetic resonance imaging (MRI) is weaker in those with dementia compared to those with mild cognitive impairment (MCI) or normal cognition. Method: We used data from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had either florbetapir amyloid PET (N=1320) of flortaucipir tau PET (N=833, 535 of whom had both). We examined the association between volumes of brain structures (FreeSurfer-v7) and standardized uptake value ratios (SUVr) for amyloid (summary cortical region, normalized to whole cerebellum) and tau (meta-temporal region, normalized to inferior cerebellar gray matter) separately, using linear regressions adjusting for age, sex, and education. We report results in overall groups and by cognitive status (normal, MCI, dementia). We display semi-partial correlations (sr, thresholded at Puncorrected<0.05), as measures of effect size. Result: Table-1 summarizes participant characteristics. The effect of amyloid on brain volumes was modest in the overall cohort, with associations strongest for inferior/middle temporal, inferior parietal, entorhinal, hippocampus, and amygdala regions (sr∼-0.2, P<0.001 all). In those with dementia, however, there were no distinct associations between amyloid and brain atrophy (Figure-1). For tau, associations in the overall cohort were similarly strongest for inferior/middle temporal, inferior parietal, entorhinal, hippocampus, and amygdala regions (sr∼-0.3, P<0.001 all). In those with dementia, associations remained strong for inferior/middle temporal regions (sr∼-0.3, P<0.001) but tau was not associated with hippocampus volumes (left, sr=-0.05, P=0.6; right, sr=-0.12, P=0.14, Figure-2); this divergence is further highlighted in select regions (inferior temporal and hippocampus) in Figure-3. Conclusion: We found that the relationship between amyloid and tau burden and atrophy was stronger in the overall cohort than in participants with dementia. This was particularly the case for medial temporal lobe structures. The effect of non-AD pathologies on medial temporal lobe atrophy is a potential explanation for the observed results.

OBJECT The purpose of this study was to explore the use of super-resolution tract density images derived from probabilistic diffusion tensor imaging (DTI) tractography of the spinal cord as an imaging surrogate for microstructural integrity and functional impairment in patients with cervical spondylosis. METHODS Structural MRI and DTI images were collected for 27 patients with cervical spondylosis with (n= 21) and without (n= 6) functional impairment as defined by the modified Japanese Orthopaedic Association Scale (mJOA). DTI was performed axially through the site of compression in a total of 20 directions with 10 averages. Probabilistic tractography was performed at 0.5-mm isotropic spatial resolution using the streamline technique combined with constrained spherical deconvolution. The following measurements were calculated for each patient: maximum tract density at the site of compression, average tract density in rostral normal-appearing spinal cord, and the ratio of maximum density to normal density. RESULTS Compared with normal tissue, the site of compression exhibited elevated fiber tract density in all patients, and a higher fiber tract density was also noted in focal areas at the site of compression in patients with functional impairment. There was a strong negative correlation between maximum tract density and mJOA score (R(2)= 0.6324, p < 0.0001) and the ratio of maximum tract density to normal tract density (R(2)= 0.6647, p < 0.0001). When grouped according to severity of neurological impairment (asymptomatic, mJOA score of 18; mild, mJOA score of 15-17; moderate, mJOA score of 11-14; and severe, mJOA score < 11), the results showed a significant difference in the ratio between severe and both no impairment (p= 0.0009) and any impairment (p= 0.036). A ratio of maximum fiber tract density at the site of compression to fiber tract density at C-2 greater than 1.45 had 82% sensitivity and 70% specificity for identifying patients with moderate to severe impairment (ROC AUC= 0.8882, p= 0.0009). CONCLUSIONS These results support the use of DTI as a surrogate for determining spinal cord integrity in patients with cervical spondylosis. Probabilistic tractography provides spinal cord microstructural information that can help discern clinical status in cervical spondylosis patients with varying degrees of neurological impairment.

OBJECTIVE The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level. METHODS Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment. A total of 183 separate MRI examinations were performed, separated by at least 3 months, and each patient had a minimum of 2 MRI scans (range 2-5 scans). Anatomical and DTI measurements were performed within the spinal cord at the C1-2 region as well as at the area of highest compression. Coefficients of variance (COVs) were compared across measurements in both reference tissue and areas of compression for anatomical measurements, fractional anisotropy (FA), and mean diffusivity (MD). The correlation between diffusion MR measures at the site of compression and evaluations of neurological function assessed using the modified Japanese Orthopaedic Association (mJOA) scale at multiple time points was evaluated. RESULTS The COVs for anatomical measurements (Torg ratio and canal diameter) were between 7% and 10%. The median COV for FA measurements at the site of compression was 9%, and for reference tissue at C1-2 it was 6%. The median COV for MD at the site of compression was approximately 12%, and for reference tissue at C1-2 it was 10%. The FA and MD measurements of C1-2 averaged 0.61 and 0.91 μm²/msec, respectively, whereas the FA and MD measurements at the site of compression averaged 0.51 and 1.26 μm²/msec, respectively. Both FA (slope = 0.037; R² = 0.3281, p < 0.0001) and MD (slope = -0.074; R² = 0.1101, p = 0.0084) were significantly correlated with the mJOA score. The FA decreased by approximately 0.032 units per mJOA unit decrease (R² = 0.2037, p < 0.0001), whereas the MD was increased by approximately 0.084 μm²/msec for every mJOA unit decrease (R² = 0.1016, p < 0.0001). CONCLUSIONS Quantitative DTI measurements of the spinal cord in patients with cervical stenosis with or without myelopathy have a median COV of 5%-10%, similar to anatomical measurements. The reproducibility of these measurements and significant correlation with functional outcome status suggest a potential role in the evaluation and longitudinal surveillance of nonoperatively treated patients. With respect to the specific DTI measurements, FA within the spinal cord appears slightly more sensitive to neurological function and more stable than measures of MD. Therefore, DTI of the spinal cord may be a clinically feasible imaging technique for longitudinally monitoring patients with cervical spondylotic myelopathy.

Cervical degenerative disease is a major cause of neck disability, but it has been understudied in patients with cervical spondylotic (CS), largely due to the fact that the neurological impairment associated with this condition tends to be the primary treatment focus. This observational study examined the cerebral functional alterations occurring in advanced cervical spondylosis and myelopathy using resting state functional MRI. Associations between functional connectivity (FC) and neck disability using the Neck Disability Index (NDI) were assessed. Results of the study demonstrated an increase in FC with increasing in neck disability in regions associated with sensorimotor system (both postcentral gyri and precentral gyri, bilaterally, with the SMA; bilateral precentral gyri and the left postcentral gyrus, with the left superior frontal gyrus; bilateral SMA and the left putamen, with the superior frontal gyri). Accounting for the difference in neurological function (mJOA score), strong connectivity between the precentral gyri and the SMA associated with the neck disability. Consistent with studies in chronic pain conditions, these findings suggest neck disability is associated with altered cerebral FC in cervical spondylosis patients.

Objective

To determine the relationship between functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and neurological impairment in patients with cervical spondylosis and healthy controls.

Methods

A total of 24 patients with cervical spondylosis with or without myelopathy and 17 neurologically intact, healthy volunteer subjects were prospectively enrolled in a cross-sectional study involving observational MRI and evaluation of neurological function using the modified Japanese Orthopedic Association (mJOA) score. Seed-to-seed connectivity and seed-to-voxel connectivity on functional MRI data were performed using a general linear model of connectivity with respect to age and mJOA score.

Results

Increased FC was observed with increasing neurological impairment in patients with cervical stenosis within sensorimotor areas, including precentral gyrus, postcentral gyrus, and supplemental motor regions, using both seed-to-seed and seed-to-voxel analyses. The anterior cingulate showed increasing connectivity with the supplemental motor area, thalamus, and cerebellum with increasing neurological function. Similarly, the thalamus, cerebellum, and putamen presented with increasing connectivity to both the bilateral precuneus and the posterior cingulate with an increasing mJOA score.

Conclusions

Patients with cervical spondylosis exhibiting neurological impairment experience changes in brain connectivity similar to that of patients with chronic traumatic spinal cord injury. These results suggest an increase in FC within sensorimotor regions with increasing neurological impairment and decreased connectivity between the cerebellum, putamen, and thalamus to the anterior and posterior cingulate and frontal lobe regions.

Objectives

Although a number of studies have implicated ischemia and hypoxia in the pathogenesis of cervical spondylosis, quantification remains difficult and the role of ischemia and hypoxia on disease progression and disease severity in human cervical spondylosis remains largely unknown. Therefore, the objective of this study was to assess spinal cord perfusion and oxygenation in human cervical spondylosis and examine the relationship between perfusion, degree of spinal cord compression, and neurological status.

Methods

Twenty-two patients with cervical spondylosis with or without myelopathy received a dynamic susceptibility contrast perfusion MRI exam consisting of a novel spin-and-gradient echo echoplanar acquisition before, during, and following gadolinium-based contrast injection. Estimation of relative spinal cord blood volume (rSCBV), the reversible relaxation rate (R₂á), and relative oxygen extraction fraction (rOEF = R₂á/rSCBV) was performed at the site of compression and compared with anterior-posterior spinal cord diameter and modified Japanese Orthopedic Association (mJOA) score, a measure of neurological impairment.

Results

rSCBV was linearly correlated with both anterior-posterior cord diameter (R² = 0.4667, P = 0.0005) and mJOA (R² = 0.2274, P = 0.0248). R₂á was linearly correlated with mJOA (R² = 0.3998, P = 0.0016) but not cord diameter (R² = 0.055; P = 0.2950). Also, rOEF was correlated with both cord diameter (R² = 0.3440, P = 0.0041) and mJOA (R² = 0.4699, P = 0.0004).

Conclusions

Results support the hypothesis that spinal cord compression results in ischemia and hypoxia, and the degree of ischemia and hypoxia is proportional to the degree of neurological impairment.

The oldest-old, those 85 years and older, are the fastest growing segment of the population and present with the highest prevalence of dementia. Given the importance of neuroimaging measures to understand aging and dementia, the objective of this study was to review neuroimaging studies performed in oldest-old participants. We used PubMed, Google Scholar, and Web of Science search engines to identify in vivo CT, MRI, and PET neuroimaging studies either performed in the oldest-old or that addressed the oldest-old as a distinct group in analyses. We identified 60 studies and summarized the main group characteristics and findings. Generally, oldest-old participants presented with greater atrophy compared to younger old participants, with most studies reporting a relatively stable constant decline in brain volumes over time. Oldest-old participants with greater global atrophy and atrophy in key brain structures such as the medial temporal lobe were more likely to have dementia or cognitive impairment. The oldest-old presented with a high burden of white matter lesions, which were associated with various lifestyle factors and some cognitive measures. Amyloid burden as assessed by PET, while high in the oldest-old compared to younger age groups, was still predictive of transition from normal to impaired cognition, especially when other adverse neuroimaging measures (atrophy and white matter lesions) were also present. While this review highlights past neuroimaging research in the oldest-old, it also highlights the dearth of studies in this important population. It is imperative to perform more neuroimaging studies in the oldest-old to better understand aging and dementia.

Introduction

Hippocampal sclerosis of aging (HS) is a common pathology often misdiagnosed as Alzheimer's disease. We tested the hypothesis that participants with HS would have a magnetic resonance imaging (MRI)-detectable hippocampal pattern of atrophy distinct from participants without HS, both with and without Alzheimer's disease neuropathology (ADNP).

Methods

Query of the National Alzheimer's Coordinating Center database identified 198 participants with MRI and autopsy. Hippocampal subfields were segmented with FreeSurfer v6. Analysis of covariance for subfield volumes compared HS+ participants to those without HS, both with ADNP (HS-/ADNP+) and without (HS-/ADNP-).

Results

HS+ participants (N = 27, 14%) showed atrophied cornu ammonis 1 (CA1; left P < .001, η_p²  = 0.14; right P = .001, η_p²  = 0.09) and subiculum (left P < .001, η_p²  = 0.139; right P = .001, η_p²  = 0.085) compared to HS-/ADNP+ (N = 100, 51%). Compared to HS-/ADNP- (N = 71, 36%), HS+ also had atrophy in subiculum (left P < .001, η_p²  = 0.235; right P = .002, η_p²  = 0.137) and CA1 (left P < .001, η_p²  = 0.137; right P = .006, η_p²  = 0.070).

Discussion

Subiculum and CA1 atrophy from clinical MRI may be a promising in vivo biomarker for HS.