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ABSTRACT: The internal carotid artery termination (CAT) ends in a T-shaped bifurcation just below the substantia innominata (SI), which contains cognitively strategic cholinergic neurons and undergoes atrophy in Alzheimer's disease (AD). This study investigated whether an elongated CAT with possible resulting encroachment into the SI would correlate with SI atrophy and with cognitive dysfunction in AD. We rated the degree of CAT encroachment upon the SI and measured SI volume on magnetic resonance imaging in 30 AD patients, 30 AD patients with subcortical small vessel disease, and 30 age-matched controls. CAT encroachment significantly correlated with SI volume after adjusting for age within the overall group and the groups with dementia. AD patients with higher CAT encroachment scores had lower SI volumes and lower attention, memory, and executive test scores. These data suggest that CAT encroachment may mechanically injure the SI, exacerbating cholinergic damage and contributing to cognitive impairment. This process may represent a possible previously underappreciated mechanism for interaction between large-vessel cerebrovascular disease and AD.
Neurobiology of aging 02/2013; · 5.94 Impact Factor
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ABSTRACT: Hippocampal volumetry derived from structural MRI is increasingly used to delineate regions of interest for functional measurements, assess efficacy in therapeutic trials of Alzheimer's disease (AD) and has been endorsed by the new AD diagnostic guidelines as a radiological marker of disease progression. Unfortunately, morphological heterogeneity in AD can prevent accurate demarcation of the hippocampus. Recent developments in automated volumetry commonly use multi-template fusion driven by expert manual labels, enabling highly accurate and reproducible segmentation in disease and healthy subjects. However, there are several protocols to define the hippocampus anatomically in vivo, and the method used to generate atlases may impact automatic accuracy and sensitivity - particularly in pathologically heterogeneous samples. Here we report a fully automated segmentation technique that provides a robust platform to directly evaluate both technical and biomarker performance in AD among anatomically unique labeling protocols. For the first time we test head-to-head the performance of five common hippocampal labeling protocols for multi-atlas based segmentation, using both the Sunnybrook Longitudinal Dementia Study and the entire Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) baseline and 24-month dataset. We based these atlas libraries on the protocols of (Haller et al., 1997; Killiany et al., 1993; Malykhin et al., 2007; Pantel et al., 2000; Pruessner et al., 2000), and a single operator performed all manual tracings to generate de facto "ground truth" labels. All methods distinguished between normal elders, mild cognitive impairment (MCI), and AD in the expected directions, and showed comparable correlations with measures of episodic memory performance. Only more inclusive protocols distinguished between stable MCI and MCI-to-AD converters, and had slightly better associations with episodic memory. Moreover, we demonstrate that protocols including more posterior anatomy and dorsal WM compartments furnish the best voxel-overlap accuracies (Dice Similarity Coefficient=0.87-0.89), compared to expert manual tracings, and achieve the smallest sample sizes required to power clinical trials in MCI and AD. The greatest distribution of errors was localized to the caudal hippocampus and alveus-fimbria compartment when these regions were excluded. The definition of the medial body did not significantly alter accuracy among more comprehensive protocols. Voxel-overlap accuracies between automatic and manual labels were lower for the more pathologically heterogeneous Sunnybrook study in comparison to the ADNI-1 sample. Finally, accuracy among protocols appears to significantly differ the most in AD subjects compared to MCI and normal elders. Together, these results suggest that selection of a candidate protocol for fully automatic multi-template based segmentation in AD can influence both segmentation accuracy when compared to expert manual labels and performance as a biomarker in MCI and AD.
NeuroImage 11/2012; · 5.89 Impact Factor
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ABSTRACT: Total knee arthroplasty (TKA) is a successful surgical technique for patients with advanced knee osteoarthritis; however, some peri-operative complications can not be predicted or avoided completely. This study aimed to investigate the factors affecting limb swelling after primary total knee arthroplasty, to guide and improve patient rehabilitation.
Using a hospital database, we retroactively analyzed the mean changes in limb circumferences of 286 consecutive patients who underwent primary unilateral total knee arthroplasty between October 2007 and August 2009. The lower limb circumference change was calculated and analyzed statistically. The influence of age, gender, body mass index, the presence of deep vein thrombosis, methods of anti-coagulation, operation time, hidden blood loss, and type of prosthesis on post-operative lower limb swelling was studied.
Swelling was most pronounced from the third to the fifth post-operative day and usually occurred in both lower limbs. Swelling was significantly more pronounced in the operated limb than in the non-operated limb. The swelling above the knee was also significantly greater than that below the knee. The change in limb circumference at 10 cm above the knee was significantly different between the patients with body mass index ≤ 25 kg/m(2) and those with body mass index > 25 kg/m(2). However, the change in limb circumference at 10 cm below the knee was not significantly different between the two groups. There was no statistically significant difference in limb swelling between different age groups (P > 0.05). Similarly, gender, methods of anti-coagulation, the presence of deep vein thrombosis, the type of prosthesis, and operation time did not significantly affect post-operative limb swelling. Multivariate linear regression showed that the factors affecting post-operative limb swelling were body mass index and hidden blood loss.
Lower limb swelling after total knee arthroplasty is related to early post-operative hidden blood loss. The patient's hemoglobin level should be monitored. The degree of limb swelling is correlated with the patient's body mass index and the amount of hidden blood loss. Early intramuscular deep vein thrombosis formation has little effect on limb swelling.
Chinese medical journal 12/2011; 124(23):3896-9. · 0.86 Impact Factor
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ABSTRACT: To investigate the relative factors for hidden blood loss (HBL) after primary total knee arthroplasty (TKA).
A retrospective study of 422 consecutive patients who underwent primary TKA between October 2007 and August 2009 was carried on. There were 60 male and 362 female patients with a mean age of 65.7 years. The HBL was calculated according to Gross formula. The effect of patient gender, age, body mass index (BMI), pre-operative diagnosis, unilateral or simultaneous bilateral TKA, tourniquet time, type of prosthesis, postoperative anticoagulation method and deep vein thrombosis (DVT) on the postoperative HBL were analyzed.
The HBL in patients underwent unilateral TKA was significantly lower than that in those underwent simultaneous bilateral TKA [(1284 ± 207) ml vs. (2248 ± 504) ml, P = 0.000]. Unvaried analysis showed that the HBL were associated with BMI, tourniquet time, prosthesis type and postoperative anticoagulation method. Multivariate linear regression analysis showed that the impact factors of postoperative HBL include BMI, tourniquet time and prosthesis type.
BMI, bilateral simultaneous TKA, tourniquet time and intercondylar open prosthesis impact the HBL after primary TKA. However, the influence of gender, age, diagnosis, postoperative anticoagulation method and DVT on the HBL are not significant.
Zhonghua wai ke za zhi [Chinese journal of surgery] 05/2011; 49(5):419-23.
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ABSTRACT: Quantification methods for white matter hyperintensities (WMH) on Magnetic Resonance Imaging are heterogeneous, deterring their application. This study compared three WMH rating scales, varying in complexity, and a volumetric method, to evaluate trade-offs between complexity and clinical utility in differentiating dementia subgroups and in correlating with cognition.
WMH were rated using the Fazekas, Age-Related White Matter Changes (ARWMC) and Scheltens scales, and segmented by computational volumetry in 108 patients with Alzheimer's Disease (AD), 23 with Mild Cognitive Impairment (MCI) and 34 normal controls (NC). Global and hippocampal atrophy, age and education, were accounted for in correlations of WMH with cognitive domains.
Intra- and inter-rater reliability were high (intraclass correlation coefficients = 0.88-0.97) across rating scales. WMH scores of all scales were highly correlated with volumes (Spearman r = 0.78-0.90, Ps < 0.001), as well as with each other (Spearman r = 0.86-0.91, Ps < 0.001). The Fazekas scale showed significant separation between AD, MCI and NC using non-parametric analysis, while the ARWMC and Scheltens' scales, and WMH volumes demonstrated significant correlations (standardized β = -0.19 to -0.24, Ps < 0.05) with cognitive domain scores using multivariate regression analysis, controlling for age, education, global and hippocampal atrophy in patients with AD.
This study suggests that the degree of complexity of WMH rating scales did not affect validation against WMH volumes, but did vary in validation against cognition. The simplest scale performed best in separating cognitive subgroups, but the more complex scales and quantification correlated better with cognitive measures, especially executive function. Hence the best choice of scale depends on the particular application.
Journal of Alzheimer's disease: JAD 01/2011; 26 Suppl 3:379-88. · 3.74 Impact Factor
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ABSTRACT: Microbleeds are hemosiderin deposits around small vessels and are well visualized with T2*-weighted gradient-recalled echo (GRE) imaging.
To determine frequency and topography of microbleeds in Alzheimer disease (AD) and to assess their association with leukoaraiosis and cognition.
Case-control cross-sectional analysis. Microbleeds were counted using GRE imaging. Leukoaraiosis was rated on T2-weighted and proton density-weighted scans using the Age-Related White Matter Changes Rating Scale (ARWMC). Neuropsychological tests indexed cognition.
The Cognitive Neurology Clinic, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Individuals with probable AD (n = 80) and healthy controls (n = 25) from a longitudinal cohort with GRE sequences as part of standard imaging protocol (2002-2006).
Microbleeds occurred in 29% of patients with AD and 12% of controls and were multiple (> 1) in 48% of patients with AD and 33% of controls. There was lobar (vs centrencephalic) predominance in 92% of AD patients, with occipital lobes accounting for 57% of these microbleeds. The ARWMC scores (P < .005) were significantly higher in AD patients with microbleeds than in those without, and microbleeds correlated with total (r = 0.39, P = .01) and parietooccipital (r = 0.28, P < .01) ARWMC scores. We were unable to demonstrate an association between microbleeds (or leukoaraiosis) and cognitive performance.
Occipital predominance of microbleeds with corresponding parietooccipital leukoaraiosis has not been well described in prior imaging studies of AD. Microbleeds were frequent, often multiple, and predicted greater leukoaraiosis. These findings illustrate the complexity of AD vasculopathy and the need for additional studies in dementia and stroke populations.
Archives of neurology 07/2008; 65(6):790-5. · 6.31 Impact Factor
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ABSTRACT: One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease.
Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing.
The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (r=0.40; P=0.02) and accounted for 12% of the variance (corrected r2). A similar model was not significant for general WMH scores.
The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.
Stroke 11/2005; 36(10):2126-31. · 5.73 Impact Factor
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ABSTRACT: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction.
Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. "Low" and "High" lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve.
Despite a similar demographic profile, subjects with a "High" lesion score performed significantly worse than the "Low" lesion score group on verbal (P = .007) and visuospatial (P = .02) memory, and on a global index of cognitive functioning (P = .001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (sigma = 0.82, P < .0001).
CHIPS is helpful in clinically predicting cognitive impairment in MS.
CNS spectrums 06/2005; 10(5):394-401. · 2.20 Impact Factor
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ABSTRACT: Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes. In vitro neuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions and beta-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs (aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs (aged 8-11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased beta-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.
Journal of Neuroscience 10/2004; 24(38):8205-13. · 7.11 Impact Factor
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ABSTRACT: Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.
Psychiatry Research 12/2002; 116(1-2):83-93. · 2.52 Impact Factor
