A new iron sensitive MR sequence (susceptibility weighted imaging -SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n=73) and cognitively normal participants (n=33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of brain microbleeds (BMB) were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p=0.035) and stable MCI (p=0.01). BMB were detected in 9 of 26 (38%) of MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants (risk ratio = 2.06 (95% confidence interval 1.37-3.12)). SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR based biomarkers for neurodegenerative diseases.
A set of twelve variables was obtained statistically in order to predict missionary success from a combination of pretraining data which included elements of personality, interpersonal skill, attitudes, and bio-graphical information. This data was gathered from structured interviews, open-ended references, and psychological tests available from each subject's application file. A screening sample of 111 vocational missionaries who had served overseas a minimum of one year was used to derive the predictors, and a calibration sample of 42 missionaries with the same qualifications was used for cross-validation purposes. The twelve significant variables selected account for 56 percent of the variance of the criterion (success). Cross-validation yielded mixed results.
The majority of mild cognitive impairment (MCI) studies use baseline and one follow-up measurement to determine the clinical course of the disorder. This report of MCI clinical course is based on the a statistical evaluation of multiple neurocognitive tests over a 60 month period in elderly normal and MCI cohorts. The data includes serial informant-based measures (Clinical Dementia Rating [CDR]) and a comprehensive battery of neuropsychological tests analyzed by two different regression methods. Twenty-nine elderly participants entered the study as neurocognitively normal; 26 remained normal, 2 progressed to MCI, and 1 progressed to dementia. Eighty-three participants entered the study as multiple domain MCI cases; 10 became normal, 46 remained MCI, and 27 progressed to dementia. Three of the 27 demented died with full necropsies performed (one case was progressive supranuclear palsy and two confirmed Alzheimer’s disease with severe cerebral amyloid angiopathy (CAA)). Without serial measures, 1 in 8 MCI could be misclassified as “stable MCI” despite reverting to normal. The stable MCI cohorts did not benefit from practice effects though the normal subjects did. Applying Classification and Regression Tree (CART) analysis enabled prediction of the endpoint status of participants from baseline values with 78.6% accuracy. The fluctuating cognitive status of the multiple domain MCI cases implies a remitting pathologic process with elements of recovery consistent with a progressive microvasculopathy such as CAA.
Advancements in clinical therapies have identified the need for biomarkers of early Alzheimer disease that distinguish the earliest stages of pathology and target those patients who are likely to gain the most benefit. The aim of this study was to characterize the longitudinal metabolic changes measured by 1H magnetic resonance spectroscopy in correlation to neuropsychologic indices of episodic memory, attention and mental processing speed, language facility, and executive function in subjects with mild cognitive impairment (MCI). Quantitative 1H magnetic resonance spectroscopy of the posterior cingulate gyrus was performed and repeated at 11.56+/-4.3 months. N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), myo-inositol (mI), and glutamate/glutamine (Glx) metabolite levels were measured, corrected for cerebrospinal fluid dilution, and ratios calculated in MCI and cognitively normal subjects. In the first study, MCI subjects showed lower NAA levels, NAA/Cho, and NAA/mI ratios and increased Cho/Cr and mI/Cr compared with controls. In the follow-up study, 36% of the MCI subjects [atypical MCI (atMCI)] showed interval increases in NAA, Cr, and Glx levels compared with 64% of MCI subjects (typical MCI) who showed an interval decrease in NAA, Cr, and Glx. Both MCI subgroups had higher Clinical Dementia Rating scores and lower scores on episodic memory, phonemic, and semantic word fluency tasks, compared with controls. The annualized rate of change in metabolic and cognitive status did not differ between normal aging and MCI subjects. atMCI subjects showed significant negative correlations between metabolite levels and executive function task scores, with NAA/mI showing a significant positive correlation with phonemic and semantic word fluency. There were no significant correlations between metabolite levels and cognitive performance in tMCI subjects; however, NAA/mI and mI/Cr were negatively correlated with executive function tasks. These results indicate 2 distinct evolving metabolite profiles that correlate with changes in executive function and can be used to differentiate MCI from normal aging.
In the long line of French Sade studies, Deleuze's essay Coldness and Cruelty marks out a special place. By discussing Masoch both in addition to and in contrast to Sade, Deleuze reveals the stakes of his book: he wants to unmask the concept of sadomasochism as a clinical nonentity. In their paper, the authors explain the arguments supporting this project and show their relation to Deleuze's reading of Bergson. They then argue that there is a second, similarly Bergsonian criticism of Freudian psychoanalysis operating in the background of Coldness and Cruelty. This more wide-ranging criticism takes Freud to task for conceiving perversion, like neurosis, in Oedipal terms. This conception, Deleuze holds, forgets that perversion and neurosis represent two different worlds that essentially have nothing to do with each other despite crossing in clinical experience.
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