Amyloid Deposition Is Greater in Cerebral Gyri than in Cerebral Sulci with Worsening Clinical Diagnosis Across the Alzheimer's Disease Spectrum.

BACKGROUND: Histopathologic studies have demonstrated differential amyloid-ß (Aß) burden between cortical sulci and gyri in Alzheimer's disease (AD), with sulci having a greater Aß burden. OBJECTIVE: To characterize Aß deposition in the sulci and gyri of the cerebral cortex in vivo among subjects with normal cognition (NC), mild cognitive impairment (MCI), and AD, and to evaluate if these differences could improve discrimination between diagnostic groups. METHODS: T1-weighted 3T MR and florbetapir (amyloid) positron emission tomography (PET) data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). T1 images were segmented and the cortex was separated into sulci/gyri based on pial surface curvature measurements. T1 images were registered to PET images and regional standardized uptake value ratios (SUVr) were calculated. A linear mixed effects model was used to analyze the relationship between clinical variables and amyloid PET SUVr measurements in the sulci/gyri. Receiver operating characteristic (ROC) analysis was performed to define amyloid positivity. Logistic models were used to evaluate predictive performance of clinical diagnosis using amyloid PET SUVr measurements in sulci/gyri. RESULTS: 719 subjects were included: 272 NC, 315 MCI, and 132 AD. Gyral and sulcal Aß increased with worsening cognition, however there was a greater increase in gyral Aß. Females had a greater gyral and sulcal Aß burden. Focusing on sulcal and gyral Aß did not improve predictive power for diagnostic groups. CONCLUSION: While there were significant differences in Aß deposition in cerebral sulci and gyri across the AD spectrum, these differences did not translate into improved prediction of diagnosis. Females were found to have greater gyral and sulcal Aß burden.

Baseline Brain Segmental Volumes in Responders and Nonresponders to Anticholinergic Therapy for Overactive Bladder Syndrome.

OBJECTIVE: Evaluate structural differences in brains of responders (R) and nonresponders (NR) to anticholinergic (AC) therapy for overactive bladder (OAB). MATERIALS AND METHODS: This was a retrospective cohort study of age matched women treated with an AC medication for OAB and underwent magnetic resonance imaging within 12 months before treatment. Data on pretreatment demographic and clinical variables and symptom severity was also collected.T1-weighted magnetic resonance images of the brain for each subject were segmented using FreeSurfer software. Structures included for analysis were cerebral cortex, white matter, subcortical gray matter, cerebellum, and brain stem.Nonresponders were defined as patients who reported less than 50% improvement after a minimum of 4 weeks on the maximum dose of the prescribed medication. Pairwise analysis between groups was performed using the Wilcoxon-Rank Sum test and Fisher exact test where appropriate. Spearman ρ was used to evaluate for correlations between neurologic structures and symptom severity. RESULTS: There were no differences in pretreatment characteristics or symptom severity between the 21 R and 18 NR. Nonresponders had lower volumes of the right caudal anterior cingulate gyrus white matter (1919 mm3 vs 2416 mm3, P = 0.008) and right parahippocampal gyrus white matter (1008 mm3 vs 1469 mm3, P = 0.001). Incontinence episode frequency showed a negative moderate correlation with the anterior cingulate gyrus white matter volume (ρ = -0.4228, P = 0.007). The right and left cerebellar cortices showed weak and moderate negative correlations to frequency of nocturia (ρ = -0.384, P = 0.02 and ρ -0.443, P = 0.005, respectively). CONCLUSION: There are measurable volumetric differences in brain structures in R and NR to AC therapy.

Genetic testing for CYP2D6 and CYP2C19 suggests improved outcome for antidepressant and antipsychotic medication.

Individuals carrying genetic variants that result in non-extensive CYP2D6 and CYP2C19 enzyme activity seem to be more prone to non-response and side-effects of psychotropic medications. Therefore, tailoring prescriptions using genetic information may improve patient outcomes. This study examined treatment outcome in psychiatric care after CYP2D6 and CYP2C19 genetic information was provided to patients and physicians. CYP2D6 and CYP2C19 genotyping, assessment of side effects and medical histories were obtained from 80 subjects who were prescribed either antidepressant or antipsychotic medications. Our measure of outcome was mainly physicians' opinions however UKU side effects scores were also used. For CYP2D6, we calculated an activity score based on genotype and psychiatric medications. Correlation analysis was performed for CYP2D6 activity scores and UKU scores. Overall, we received supportive responses from physicians who enrolled patients in our study. Notably, while almost every fourth physician reported improvement in patient outcome, not a single physician indicated that their patient's symptoms worsened after they had used a pharmacogenetic report to guide treatment. We did not observe statistically significant differences in side effects. Overall, our results suggest improved patient outcome following pharmacogenetic testing; nonetheless, more research is required to assess the exact benefit of pharmacogenetics in clinical practice.

Travel medicine physician adherence to guidelines for the emergency self treatment of malaria.

Few studies have examined emergency self treatment (EST) antimalarial prescribing patterns. 110 physician-members of the Travel Medicine Society of Ireland and British Global and Travel Health Association participated in this study. There was a trend towards the prescription of EST for travel to remote low-risk malaria areas; for long-term residents living in low-risk areas; and for frequent travellers to low-risk areas. This study provides insights into the use of EST in travellers' malaria.

Physicians' opinions following pharmacogenetic testing for psychotropic medication.

Pharmacogenetics seeks to improve patient drug response and decrease side effects by personalizing prescriptions using genetic information. Since 2012, by one estimate, the number of patients who have had pharmacogenetic testing has doubled and this number is expected to double again by 2015. Given the increasing evidence for genetic influences on treatment response, we deemed it important to study physicians' opinions of pharmacogenetic testing. Surveys were completed by 168 Canadian physicians who had ordered at least one pharmacogenetic test (in particular for CYP2D6 or CYP2C19) for the prescription of psychiatric medication. Our results indicated that 80% of respondents believe genetic testing would become common standard in psychiatric drug treatment and 76% of respondents reported satisfactory or higher than satisfactory understanding of the pharmacogenetic report provided. Significantly more male physicians believed they had a higher understanding of the pharmacogenetic report compared to female physicians. To our knowledge, this is the only study that has assessed physicians' opinions of pharmacogenetic testing for psychotropic medication after they had received a pharmacogenetic report. Our results demonstrate a positive opinion of physicians on pharmacogenetics and indicate great potential for future clinical application.