Medial temporal lobe atrophy and APOE genotype do not predict cognitive improvement upon treatment with rivastigmine in Alzheimer's disease patients

BACKGROUND: Only a subgroup of subjects with probable AD shows cognitive improvement after treatment with cholinesterase inhibitors. OBJECTIVES: To investigate whether atrophy of the medial temporal lobe and the apolipoprotein E (APOE) genotype could predict cognitive improvement in subjects with probable AD treated with rivastigmine. METHODS: 121 subjects with mild to moderate probable AD were treated for 26 weeks with escalating doses of rivastigmine. Outcome measures were change on the MMSE and the ADAS-Cog between baseline and follow-up and treatment response defined as at least 2 points improvement on the MMSE or at least 4 points improvement on the ADAS-Cog. The study was an open-label multi-centre study in The Netherlands. RESULTS: Subjects with medial temporal lobe atrophy (MTLA) tended to show more decline on the MMSE after correction for age, sex, education, baseline cognitive score, and dosage at week 26 compared with subjects without MTLA (p = 0.08). A significant interaction between MTLA and dosage at week 26 existed for change on the MMSE and ADAS-Cog: subjects with MTLA showed more cognitive decline than subjects without MTLA only in the group of patients who received a low dosage at week 26. MTLA was not associated with treatment response. The APOE genotype was not associated with change on the MMSE or ADAS-Cog or with treatment response. CONCLUSIONS: MTLA and the APOE genotype are not clinically useful predictors of cognitive response in subjects with probable AD who are treated with rivastigmine.     

Cuff electrode implantation around the sciatic nerve is associated with an upregulation of TNF-alpha and TGF-beta 1

Epineurial fibrosis, fiber loss, limited reproducibility of recordings and variability of stimulation conditions have been documented after extraneural cuff electrode implantation. These morphological and electrophysiological modifications could be due to the local release of cytokines. We report the expression of two cytokines, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in the rat sciatic nerve after 'cuff' implantation for 18 h, 7 days and 1 month. Immunohistochemical and Western blot analyses showed a transient upregulation of TNF-alpha, during the first week, and a prolonged increase of TGF-beta1, over the 1-month period duration of this study. Considering the known pro-inflammatory roles of TNF-alpha and the pro-fibrotic action of TGF-beta, our results strongly suggest that these cytokines may contribute to nerve alterations occurring within the acute and sub-acute phases after cuff electrode implantation.     

S-100B concentration is not related to neurocognitive performance in the first month after mild traumatic brain injury

The serum concentration of S-100B is reported to reflect the severity of brain damage. The purpose of this study was to determine whether elevated serum S-100B concentrations were related to neuropsychological test performance of patients in the subacute phase of recovery from mild traumatic brain injury (TBI). S-100B concentrations were measured in blood samples taken within 6 h after TBI. Serum S-100B was estimated using an immunoluminometric assay. Cognitive speed and memory were assessed with neuropsychological tests at a median of 13 days (range 7-21 days) after injury. The two groups, formed on a median split of initial serum S-100B concentrations (>or<0.22 microg/l) did not differ in age or education. The neuropsychological performance of the TBI patients was also compared with that of a healthy control group. Cognitive speed and memory performance of mild TBI patients were inferior compared to those of healthy subjects. There were no significant differences within the TBI group when serum S-100B concentration was taken into consideration. The findings suggest that serum S-100B levels after mild TBI are not predictive of neuropsychological performance in the subacute stage of recovery.     

Behavioral problems in dementia patients and salivary cortisol patterns in caregivers

This study examines cortisol profiles in caregivers of dementia patients and their relationship to patients' behavioral problems. Salivary cortisol profiles and cortisol response to awakening were measured in 57 caregivers and 55 noncaregiver comparison subjects. Caregivers showed significantly higher levels of cortisol at the time of morning awakening than did comparison subjects, with a smaller increase after awakening. A higher cortisol awakening response was found in caregivers of patients with high versus low levels of behavioral and psychological symptoms of dementia (BPSD). Elevated morning cortisol levels could predispose caregivers to negative health consequences, with caregivers of patients with BPSD at greater risk.     

Combined quantitative dynamic contrast-enhanced MR imaging and (1)H MR spectroscopic imaging of human prostate cancer

PURPOSE: To differentiate prostate carcinoma from healthy peripheral zone and central gland using quantitative dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and two-dimensional (1)H MR spectroscopic imaging (MRSI) combined into one clinical protocol. MATERIALS AND METHODS: Twenty-three prostate cancer patients were studied with a combined DCE-MRI and MRSI protocol. Cancer regions were localized by histopathology of whole mount sections after radical prostatectomy. Pharmacokinetic modeling parameters, K(trans) and k(ep), as well as the relative levels of the prostate metabolites citrate, choline, and creatine, were determined in cancer, healthy peripheral zone (PZ), and in central gland (CG). RESULTS: K(trans) and k(ep) were higher (P < 0.05) in cancer and in CG than in normal PZ. The (choline + creatine)/citrate ratio was elevated in cancer compared to the PZ and CG (P < 0.05). While a (choline + creatine)/citrate ratio above 0.68 was found to be a reliable indicator of cancer, elevated K(trans) was only a reliable cancer indicator in the diagnosis of individual patients. K(trans) and (choline + creatine)/citrate ratios in cancer were poorly correlated (Pearson r(2) = 0.07), and thus microvascular and metabolic abnormalities may have complementary value in cancer diagnosis. CONCLUSION: The combination of high-resolution spatio-vascular information from dynamic MRI and metabolic information from MRSI has excellent potential for improved localization and characterization of prostate cancer in a clinical setting. J. Magn. Reson. Imaging 2004;20:279-287. Copyright 2004 Wiley-Liss, Inc.     

Cost-analysis of staging methods for lymph nodes in patients with prostate cancer: MRI with a lymph node-specific contrast agent compared to pelvic lymph node dissection or CT

The aim of this study was to compare the costs of three strategies in patients with prostate cancer in a specific setting: firstly, a strategy including MR lymphography (MRL) in which pelvic lymph node dissection (PLND) is foregone in case of a negative result. The second strategy involves computed tomography (CT) followed by a biopsy or PLND. The third strategy consists of PLND without imaging beforehand. A decision analytic model was constructed. This model represented the diagnostic process for patients with prostate cancer and intermediate or high risk for nodal metastases, comparing the costs of the three strategies. Cost analysis was done from the health care perspective. The model indicated that the expected costs for the MRL strategy were €2,527. The expected costs for the strategy using CT were €3,837 and for PLND €3,994. These results show that potential savings performing MRL instead of CT were €1,310 and €1,467 for PLND. Sensitivity analyses show that variation in costs of PLND was most influential on the costs of all strategies. However, the overall savings pattern did not alter. Average costs of MRL staging in our institution are less than for CT and PLND in staging lymph nodes of patients with prostate cancer and who are intermediate or high risk for nodal metastases.     

A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time

Voxel-based morphometry (VBM) was used to examine the relation between age and gray matter density cross-sectionally and to study the association between gray matter density and longitudinal decline in performance on cognitive tests in healthy, non-demented elderly individuals. Participants were neuropsychologically tested at baseline and again after 3 years. Thirty-seven subjects (mean age 72.5 years) who showed a decline in cognitive test performance at follow-up were compared with 38 individually matched control subjects (mean age 71.8 years) whose performance did not change over time. Magnetic resonance imaging scans were acquired at follow-up and individual differences in regional gray matter density were examined with VBM. The largest age effects were found in various regions in the prefrontal cortex, the (medial) temporal lobes and the striate cortex. Longitudinal cognitive decline was associated with decreased gray matter density in prefrontal areas, the (medial) temporal lobes and the posterior parietal cortex. These findings suggest that prefrontal and temporal cortical regions are of particular relevance both in aging and age-related cognitive decline in healthy elderly individuals.     

The Role of MRI in Invasive Lobular Carcinoma

PURPOSE: To determine the value of MR imaging in the detection and measurement of tumor size in patients with invasive lobular carcinoma (ILC) compared to mammography and ultrasound. MATERIALS AND METHODS: From 36 cases of ILC in 34 patients who were surgically treated, the pre-operative imaging measurements, being mammography, ultrasound and contrast enhanced MR, were retrospectively re-evaluated for tumor detection and size. Findings were compared with pathology. Two radiologists were used for evaluation of the mammograms, the other imaging modalities were only evaluated by one radiologist. The Pearsons correlation test was used to determine the correlation between histopathological and imaging measurements for each imaging modality. RESULTS: For mammography, ultrasound and MRI the false negative scores were respectively 14%, 3% and 0%. The percentage for underestimated, correctly estimated and overestimated measurements on imaging were 56%, 33% and 11% for radiologist 1 and 50%, 33% and 17% for radiologist 2 on mammography. For ultrasound and MRI these percentages were respectively 53%, 47%, 0% and 14%, 75%, 11%. The correlation coefficients for mammography were respectively r = 0.34 (p < 0.05) and r = 0.27 (p > 0.05) for both radiologists, for Ultrasound r = 0.24 (p > 0.05) and for MRI r = 0.81 (p < 0.01). CONCLUSION: Of the three imaging modalities contrast enhanced MR has the lowest false negative rate in detecting ILC and has the highest accuracy in measuring the size of the ILC. MR could play a key role in the pre-operative work-up for accurate tumor size determination.     

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging

PURPOSE: To prospectively evaluate ferumoxtran-10-enhanced magnetic resonance (MR) imaging for nodal staging in patients with urinary bladder cancer. MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer were enrolled. Results of MR imaging performed before and after injection of ferumoxtran-10 were compared with histopathologic results in surgically removed lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetization-prepared rapid acquisition gradient-echo (voxel size, 1.4 x 1.4 x 1.4 mm) and T2*-weighted gradient-echo (voxel size, 0.8 x 0.8 x 3.0 mm) sequences were performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per kilogram of body weight). On precontrast images, lymph nodes were defined as malignant by using size and shape criteria (round node, >8 mm; oval, >10 mm axial diameter). On postcontrast images, nodes were considered benign if there was homogeneous decrease in signal intensity and malignant if decrease was absent or heterogeneous. Qualitative evaluation was performed on a node-to-node basis. Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic regression analysis. RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were matched and correlated with results of node dissection. Of these, 122 were benign and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity, specificity, and positive and negative predictive values on precontrast images were 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcontrast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic metastases, sensitivity and negative predictive value improved significantly at postcontrast compared with those at precontrast imaging, from 76% to 96% (P < .001) and from 91% to 98% (P < .01), respectively. At postcontrast imaging, metastases (4-9 mm) were prospectively found in 10 of 12 normal-sized nodes (<10 mm); these metastases were not detected on precontrast images. Postcontrast images also showed lymph nodes that were missed at pelvic node dissection in two patients. CONCLUSION: Ferumoxtran-10-enhanced MR imaging significantly improves nodal staging in patients with bladder cancer by depicting metastases even in normal-sized lymph nodes.     

Atypical cognitive profile in patients with depression after myocardial infarction

BACKGROUND: We evaluated the cognitive profile of 48 patients with major depression following their first myocardial infarction (MI). METHODS: The cognitive performance of the patients was compared with the performance of 48 non-depressed MI patients and 48 healthy controls. RESULTS: Depressed MI patients performed slower on a simple cognitive speed related measure compared with non-depressed MI patients and healthy controls. Attention and speed-related aspects of cognitive functioning were not affected. Surprisingly, (depressed) MI patients showed even better performances with respect to memory function. LIMITATION: No patients with non-MI-related depression were included. CONCLUSIONS: The cognitive profile of major depression after MI differs from that of non-cardiac-related depressive disorder, as described in the literature. This may reflect a different etiology of post MI depression from non-cardiac-related depression.